2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

Ovarian cancer (OC) is the second most common type of gynecological malignancy. Platinum (Pt)-based chemotherapy is the standard of care for OC, but toxicity and acquired chemoresistance has proven challenging. Recently, we reported that sensitivity to platinum was significantly reduced in a co-culture of OC cells with MSC. To discover compounds capable of restoring platinum sensitivity, we screened a number of candidates and monitored ability to induce PARP cleavage. Moreover, we monitored platinum uptake and expression of ABC transporters in OC cells. Our results showed that 2-hydroxyestradiol (2HE2), a metabolite of estradiol, and dasatinib, an Abl/Src kinase inhibitor, were significantly effective in overcoming MSC-mediated platinum drug resistance. Dasatinib activity was dependent on ERK1/2 activation, whereas 2HE2 was independent of the activation of ERK1/2. MSC-mediated platinum drug resistance was accompanied by reduced intracellular platinum concentrations in OC cells. Moreover, MSC co-cultured with OC cells resulted in downregulation of the expression of cellular transporters required for platinum uptake and efflux. Exposure to 2HE2 and other modulators resulted in an increase in intracellular platinum concentrations. Thus, 2HE2 and dasatinib might act as sensitizers to restore platinum drug sensitivity to OC cells and thus to limit TME-mediated chemoresistance in OC.     

Dislocation density crystalline plasticity modeling of lath martensitic microstructures in steel alloys

A three-dimensional multiple-slip dislocation density-based crystalline formulation, specialized finite-element formulations and Voronoi tessellations adapted to martensitic orientations were used to investigate large strain inelastic deformation modes and dislocation density evolution in martensitic microstructures. The formulation is based on accounting for variant morphologies and orientations, retained austenite and initial dislocation densities that are uniquely inherent to martensitic microstructures. The effects of parent austenite orientation and retained austenite were also investigated for heterogeneous fcc/bcc crystalline structures. Furthermore, the formulation was used to investigate microstructures mapped directly from SEM/EBSD images of martensitic steel alloys. The analysis indicates that variant morphology and orientations have a direct effect on dislocation density accumulation and inelastic localization in martensitic microstructures, and that lath directions, orientations and arrangements are critical characteristics of high strength martensitic deformation and behavior.     

First synthesis and structure of beta-ketoimine calix[4]arenes: complexation and extraction studies

The synthesis of a new series of beta-ketoimine calix[4]arene derivatives is described. The reaction of calix[4]arene or p-tert-butylcalix[4]arene with bromoacetonitrile or bromobutyronitrile afforded di-, tri-, and tetranitrile calixarene derivatives (3-8, 3a), which were then reduced into the corresponding amine (9-13, 3b). The condensation of these aminocalixarenes with acetylacetone led to six beta-ketoimine calix[4]arene derivatives (14-18, 3c) as a class of selective receptors toward transition metals. Molecular structures of 4, 7, and 17 have been determined by X-ray diffraction. The packing of 17 revealed a network of intramolecular and intermolecular hydrogen bonds. The complexation properties of receptors 15, 17, and 3c toward different metal ions have been investigated by UV-vis titrations in organic media. The stoichiometries of complexes with 17 were determined by both the mole ratio method and Job plots. These novel receptors selectively complex Cu2+, Hg2+, and Ag+. Moreover, the extraction properties of 17 toward cations have been studied by liquid-liquid extraction and atomic absorption spectrometry. Compound 17 has good affinity and selectivity toward Pb2+.     

Synthesis and photochemical properties of novel pentamethylated norbornadiene containing polyimides

A novel pentamethylated norbornadiene (NBD) based dianhydride, α,α′‐bis‐(3,4,5,6,7‐pentamethylcyclopenta‐2,4‐dienyl)meta‐xylene‐1,2‐dianhydride (3), was prepared from α,α′‐bis‐(pentamethylcyclopentadienyl)meta‐xylene (1) and acetylene dicarboxylic acid. The bis‐adduct formed via Diels–Alder reaction afforded tetra‐acid (2), which was chemically cyclodehydrated to lead the targeted dianhydride (3). New polyimides containing NBD moieties in the main chain were prepared from the dianhydride monomer (3) and various aromatic diamines. The chemical structure of the polymers was confirmed by both ¹H and ¹³C NMR analysis. Their Molecular weights were also measured by SEC. All of these polyimides are soluble at room temperature in common organic solvents, such as chloroform, dichloromethane, THF, DMSO, DMF, and NMP, and show good thermal stabilities. The photochemical isomerization of the NBD into quadricyclane (QC) was investigated by UV/vis spectrophotometry from polymer films using visible sunlight as irradiation source. It was found that the kinetic rate of the conversion NBD‐QC which proceeded smoothly is a first kinetic order. The stored energies released by the transformation of QC groups into NBD ones of the irradiated polymer films were also evaluated by DSC measurement and were found to be around 90 kJ mol^?1. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Performance Evaluation and Effectiveness of the Reverberation Room

This research presents a thorough evaluation of the reverberation room at Acoustics Laboratory in National Institute of Standards (NIS) according to the related international standards. The evaluation aims at examining the room performance and exploring its effectiveness in the frequency range from 125 Hz to 10000 Hz according to the international standard requirements. The room, which was designed and built several years ago, is an irregular rectangular shape free from diffusers. Its volume is about 158.84 m³, which meets the requirement of the ISO 354 standard L_max < 1.9V^1/3. Cut-off frequencies of one and one-third octave are 63 Hz and 100 Hz respectively; however Schroder frequency is 400 Hz. Calculations of cut-off frequency and modal density showed adequate modes that give acceptable uniformity starting comfortably from frequency of 125 Hz. The room has a reverberation time that is suitable for its size over the frequency range of interest. The room sound absorption surface area and its sound absorption coefficient satisfy the criteria given in ISO 3741 and ISO 354. There is an accepted diffuse sound field inside the room due to the standard deviation of measured sound level, which is less than 1.5 dB over all the frequency range. The only exception was 125 Hz which may be due to a lack of diffusivity of the sound field at this frequency. The evaluation proves that the NIS reverberation room is in full agreement with the international standards, which in turns qualifies the room to host measurements inside without concerns.     

Elaboration of sponge-like biodegradable cationic particles via double-emulsion solvent evaporation

Researchers work on different optimization methods to come up with preparation methods, which show the desired or targeted outcomes. Moreover, nowadays, research is more focused on developing formulations which contain biodegradable polymers. The objective of the present systematic study was to achieve the abovementioned goals by using a cationic ammonio methacrylate copolymer (Eudragit® RS100). A Double-emulsion solvent evaporation technique was used. This methodology was chosen because the particles formed by this method allow encapsulation of both hydrophilic and hydrophobic active molecules. It also has applications in diverse fields such as drug delivery, food, cosmetics, and pharmaceutical industries.

The aim of this research work was to investigate the influence of various process control parameters, such as stabilizer chemical nature and amount, ultra Turrax® stirring speed and time, the morphology, size, and size distribution of the final dispersions. Then, the prepared particles were characterized using a Scanning Electron Microscope (SEM) and a Laser Diffraction Particle Size Analyzer. This study helped us to know which parameters have a drastic effect on the colloidal properties of the particles.     

An orienteering model for the search and rescue problem

In this paper, we propose a new model for the search and rescue problem. We focus on the case of a single airborne search asset through a connected space and continuous time with a maximum travel time \(T\) . The intent is to maximize the detection of a cooperative target (search and rescue). The proposed model is based on the assumption of existing a priori information (e.g., result of information fusion process) to establish a spatial distribution of probability of containment in possible geographic locations. The possibility area is defined using a cut threshold on the probability of containment and the search path as well as the allocation of the level of effort to each region in the search space is obtained based on an orienteering model. We illustrate the application of the proposed model on an empirical example.     

On a transport operator arising in growing cell populations II. Cauchy problem

This paper deals with Rotenberg's models of cell populations with general boundary conditions. It is shown, first, that the associated Cauchy problem is governed by a C₀‐semigroup. Second, we have proved that if the boundary operator is positive, the transport semigroup is irreducible. And finally, a spectral decomposition of the solution into an asymptotic term was derived. Copyright © 2004 John Wiley & Sons, Ltd.