miRNAs Participate in the Regulation of Oxidative Stress-Related Gene Expression in Endometrioid Endometrial Cancer

Reactive oxygen species are formed as by-products of normal cell metabolism. They are needed to maintain cell homeostasis and signaling, which is possible due to defense systems. Disruption of this balance leads to oxidative stress that can induce cancer. Redox regulation by miRNAs may be a potential therapeutic target. The aim of the study was to assess the activity of genes associated with oxidative stress in endometrial cancer and to determine their relationship with miRNAs. The study included 45 patients with endometrioid endometrial cancer and 45 without neoplastic changes. The expression profile of genes associated with oxidative stress was determined with mRNA microarrays, RT-qPCR and ELISA. The miRNA prediction was performed based on the miRNA microarray experiment and the mirDB tool. PRDX2 and AQP1 showed overexpression that was probably not related to miRNA activity. A high level of PKD2 may be the result of a decrease in the activity of miR-195-3p, miR-20a, miR-134. A SOD3 level reduction can be caused by miR-328, miR-363. In addition, miR-363 can also regulate KLF2 expression. In the course of endometrial cancer, the phenomenon of oxidative stress is observed, the regulation of which may be influenced by miRNAs.     

Structure–Function Relationships in the Human P-Glycoprotein (ABCB1): Insights from Molecular Dynamics Simulations

P-Glycoprotein (P-gp) is a transmembrane protein belonging to the ATP binding cassette superfamily of transporters, and it is a xenobiotic efflux pump that limits intracellular drug accumulation by pumping compounds out of cells. P-gp contributes to a reduction in toxicity, and has broad substrate specificity. It is involved in the failure of many cancer and antiviral chemotherapies due to the phenomenon of multidrug resistance (MDR), in which the membrane transporter removes chemotherapeutic drugs from target cells. Understanding the details of the ligand–P-gp interaction is therefore critical for the development of drugs that can overcome the MDR phenomenon, for the early identification of P-gp substrates that will help us to obtain a more effective prediction of toxicity, and for the subsequent outdesign of substrate properties if needed. In this work, a series of molecular dynamics (MD) simulations of human P-gp (hP-gp) in an explicit membrane-and-water environment were performed to investigate the effects of binding different compounds on the conformational dynamics of P-gp. The results revealed significant differences in the behaviour of P-gp in the presence of active and non-active compounds within the binding pocket, as different patterns of movement were identified that could be correlated with conformational changes leading to the activation of the translocation mechanism. The predicted ligand–P-gp interactions are in good agreement with the available experimental data, as well as the estimation of the binding-free energies of the studied complexes, demonstrating the validity of the results derived from the MD simulations.     

Immunohistochemical Evaluation of Periodontal Regeneration Using a Porous Collagen Scaffold

(1) Aim: To immunohistochemically evaluate the effect of a volume-stable collagen scaffold (VCMX) on periodontal regeneration. (2) Methods: In eight beagle dogs, acute two-wall intrabony defects were treated with open flap debridement either with VCMX (test) or without (control). After 12 weeks, eight defects out of four animals were processed for paraffin histology and immunohistochemistry. (3) Results: All defects (four test + four control) revealed periodontal regeneration with cementum and bone formation. VCMX remnants were integrated in bone, periodontal ligament (PDL), and cementum. No differences in immunohistochemical labeling patterns were observed between test and control sites. New bone and cementum were labeled for bone sialoprotein, while the regenerated PDL was labeled for periostin and collagen type 1. Cytokeratin-positive epithelial cell rests of Malassez were detected in 50% of the defects. The regenerated PDL demonstrated a larger blood vessel area at the test (14.48% ± 3.52%) than at control sites (8.04% ± 1.85%, p = 0.0007). The number of blood vessels was higher in the regenerated PDL (test + control) compared to the pristine one (p = 0.012). The cell proliferative index was not statistically significantly different in pristine and regenerated PDL. (4) Conclusions: The data suggest a positive effect of VCMX on angiogenesis and an equally high cell turnover in the regenerated and pristine PDL. This VCMX supported periodontal regeneration in intrabony defects.     

SkaSim – Skalierbare HPC‐Software für molekulare Simulationen in der chemischen Industrie

This article outlines advances in molecular modeling and simulation using massively parallel high‐performance computers (HPC). In the SkaSim project, partners from the HPC community collaborated with users from science and industry. The aim was to optimize the prediction of thermodynamic property data in terms of efficiency, quality and reliability using HPC methods. In this context, various topics were dealt with: atomistic simulation of homogeneous gas bubble formation, surface tension of classical fluids and ionic liquids, multicriteria optimization of molecular models, the development of the molecular simulation codes ls1 mardyn and ms2, atomistic simulation of gas separation processes, molecular membrane structure generators, transport resistors and the evaluation of predictive property data models based on specific mixture types.     

SPIFI: a direct-detection imaging spectrometer for submillimeter wavelengths

The South Pole Imaging Fabry-Perot Interferometer (SPIFI) is the first instrument of its kind-a direct-detection imaging spectrometer for astronomy in the submillimeter band. SPIFI's focal plane is a square array of 25 silicon bolometers cooled to 60 mK; the spectrometer consists of two cryogenic scanning Fabry-Perot interferometers in series with a 60-mK bandpass filter. The instrument operates in the short submillimeter windows (350 and 450 microm) available from the ground, with spectral resolving power selectable between 500 and 10,000. At present, SPIFI's sensitivity is within a factor of 1.5-3 of the photon background limit, comparable with the best heterodyne spectrometers. The instrument's large bandwidth and mapping capability provide substantial advantages for specific astrophysical projects, including deep extragalactic observations. We present the motivation for and design of SPIFI and its operational characteristics on the telescope.     

In vitro biotransformation of (R)- and (S)-thalidomide: application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites

Circular dichroism (CD) spectroscopy was successfully used for the stereochemical characterization of the hydroxylated metabolites formed during the in vitro biotransformation of (R)- and (S)-thalidomide. Incubation extracts of the individual enantiomers were analyzed by HPLC on an achiral stationary phase combined with CD detection. The CD data of the almost enantiopure eluates of the metabolites were compared with the CD spectra quantum chemically calculated for the respective structures. The results allowed us a reliable determination of the absolute stereostructure for all of the metabolites. The chiral center of thalidomide is unaffected by the stereoselective biotransformation process. (3'R,5'R)-trans-5'-hydroxythalidomide is the main metabolite of (R)-thalidomide, which epimerizes spontaneously to give the more stable (3'S,5'R)-cis isomer. On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide.     

Abusive testing of large Li/SOCl2 cells

Results are reported of various abuse tests conducted with lithium-thionyl chloride primary batteries of 2 000 A h and 10 000 A h capacity. The mechanical abuse tests, such as shock and vibration, showed that the large prismatic cells can now be built to satisfy typical military requirements. The thermal abuse tests showed that the cells can withstand a considerable overheating or a thermal shock treatment, as long as provisions were made for the thermal expansion of the electrolyte. The electrochemical abuse tests showed that the cells could be overdischarged (driven in reverse beyond discharge) to an equivalent of up to 50% of the discharge capacity with no adverse effects. The short circuit test, as a combination of the electrochemical and thermal abuse, was performed with no rupture, explosion or any other adverse effects on the surroundings.     

Fractal substructure of a nanopowder generated by repeated fragmentation and sedimentation: the rôle of the dust

Packings of cohesive nanoparticles, that is nanopowders, may be obtained as the result of repeated fragmentation–reagglomeration cycles (Schwager et al. in Phys Rev Lett 100:218002, 2008) such that the resulting sediment reveals a fractal structure. The size distribution of the fragments after a fragmentation step is a superposition of a narrow distribution of large particles (chunks) whose size is determined by the cutting length and a power-law distribution for small particles, representing scale invariant dust. It was shown that the exponent of the power-law, \(\tau \), is in non-trivial relation to the fractal dimension, \(d_f\), via \(d_f(2-\tau )=1\). This poses the question for the structure of the sediment created by repeated fragmentation–reagglomeration cycles when the dust particles are excluded from the reagglomeration step. We found that even in this case, repeated fragmentation–reagglomeration cycles yield a sediment of fractal structure with slightly reduced fractal dimension while the dust exponent, \(\tau \), remains unchanged.     

INFERENCE PROCEDURES FOR FUZZY KNOWLEDGE REPRESENTATION SCHEME

This article presents a formal model of the knowledge representation scheme based on the fuzzy Petri net (FPN) theory. The model is represented as a 13-tuple consisting of the components of the FPN, two functions that give semantic meanings to the scheme and a set of contradictions. For the scheme, called the knowledge representation scheme based on the fuzzy Petri nets theory (KRFPN) the fuzzy inheritance and fuzzy recognition-inference procedures based on the dynamical properties of the FPN, are described in detail. The upper-time complexity of both the proposed inference algorithms is O(nm), where n is the number of places (concepts) and m is the number of transitions (relations) in the scheme. Illustrative examples of the fuzzy inheritance and the fuzzy recognition algorithms for the knowledge base, designed by the KRFPN, are given.