Pan-Cancer Prediction of Cell-Line Drug Sensitivity Using Network-Based Methods

The development of reliable predictive models for individual cancer cell lines to identify an optimal cancer drug is a crucial step to accelerate personalized medicine, but vast differences in cancer cell lines and drug characteristics make it quite challenging to develop predictive models that result in high predictive power and explain the similarity of cell lines or drugs. Our study proposes a novel network-based methodology that breaks the problem into smaller, more interpretable problems to improve the predictive power of anti-cancer drug responses in cell lines. For the drug-sensitivity study, we used the GDSC database for 915 cell lines and 200 drugs. The theory of optimal mass transport was first used to separately cluster cell lines and drugs, using gene-expression profiles and extensive cheminformatic drug features, represented in a form of data networks. To predict cell-line specific drug responses, random forest regression modeling was separately performed for each cell-line drug cluster pair. Post-modeling biological analysis was further performed to identify potential biological correlates associated with drug responses. The network-based clustering method resulted in 30 distinct cell-line drug cluster pairs. Predictive modeling on each cell-line-drug cluster outperformed alternative computational methods in predicting drug responses. We found that among the four drugs top-ranked with respect to prediction performance, three targeted the PI3K/mTOR signaling pathway. Predictive modeling on clustered subsets of cell lines and drugs improved the prediction accuracy of cell-line specific drug responses. Post-modeling analysis identified plausible biological processes associated with drug responses.     

Thermosensitive folic acid-targeted poly (ethylene-<Emphasis Type="Italic">co</Emphasis>-vinyl alcohol) hemisuccinate polymeric nanoparticles for delivery of epirubicin to breast cancer cells

A novel thermosensitive folic acid (FA)-targeted succinylated poly (ethylene-co-vinyl alcohol) (EVOH) (EVOHS-FA) nanocarrier was synthesized for the specific delivery of epirubicin (EPI) to MCF-7 breast cancer cell line. Three different ratios of synthesized EVOH-Suc were reacted with FA. The structure of the desired products (EVOHS₄₀-FA, EVOHS₆₀-FA and EVOHS₈₀-FA) was confirmed by ¹H NMR and FTIR techniques. Nanoparticles were obtained by nano-precipitation procedure using DMSO/H₂O as solvent/anti-solvent. The particle size, zeta potential, entrapment efficacy and in vitro release profile of the final formulations in different temperatures were measured. The optimized nanoparticles had the particle size of 214 ± 8.5 nm, zeta potential of ?29.6 mV, PDI of 0.198 ± 0.04, and a high encapsulation efficiency that released the drug efficiently within 450 h at the temperature of 40 °C compared to 37 °C. The morphology of nanoparticles was studied by scanning electron microscopy. The in vitro cytotoxicity was evaluated using the MTT assay on MCF-7 cell lines in response to temperatures of 37 and 40 °C. The MTT assay indicated that the targeted nanoparticles carrying EPI were significantly more cytotoxic than the non-targeted nanoparticles and the free drug at 40 °C.     

Proposal of an equivalent linearization method to predict seismic hysteretic energy demand considering stiffness degradation effects

To overcome complexities and shortcomings of previous studies, a new method is proposed to derive an equivalent linear model for predicting seismic hysteretic energy demand of bilinear single degree of freedom (SDOF) models. A new displacement spectrum is defined, which represents hysteretic energy. It is found that by increasing initial period and damping of a nonlinear system in the correct proportion and defining a linear model with these characteristics, the new developed displacement can be achieved. Error minimization is applied through an algorithm to find the optimum equivalent period corresponding to an equivalent damping utilizing two sets of far‐field and near‐field earthquakes. To analyze the effects of stiffness degradation, the proposed algorithm has been implemented on modified Clough hysteretic model as well. Comparing the results, effects of stiffness degradation on the ratio of equivalent to initial period is evident in the short period range, while with increasing initial period, the effect can almost be neglected at higher values of ductility. Nonlinear regression analysis is carried out to provide the equations for predicting equivalent linear parameters as a function of ductility. Despite the previous predictive equations, the proposed model is independent of earthquake characteristics and response‐related parameters, which has increased efficiency as well as simplicity.     

A comparative study of ethylene polymerization by bis(aminotropone) Ti catalysts

A series of titanium aminotropone complexes bearing a pair of chelating [O–N] ligands have been synthesized and used for polymerization of ethylene successfully. Ethylene polymerization reactions were carried out at different conditions using the prepared catalysts. The activities for ethylene polymerization were significantly dependent on the catalyst structure. The polymerization activity increased with increasing of the both monomer pressure and [MAO]:[Ti] ratio. The highest activity of the catalysts was obtained at about 30–40 °C. It was demonstrated that unlike the high performance Ti–FI catalysts, bis(aminotropone) Ti catalysts do not require the presence of steric bulk in close proximity to the oxygen moiety. Introduction of the bulky alkyl substitution next to the oxygen moiety decreased the activity of the catalysts. Density Functional Theory (DFT) studies reveal that the active species derived from these catalysts normally possess higher electrophilicity nature compared with those produced using bis(phenoxy-imine) Ti catalysts (Ti–FI catalysts). Hydrogen was used as the chain transfer agent. The activities of the catalysts were increased with hydrogen concentration to some extent, but the M _v values of the obtained polymers were decreased. Crystallinity and melting point of the obtained polymer were between 42–62% and 102–124 °C, respectively. Higher pressure increased both the crystallinity and the M _v values of the resulting polymers. The catalyst 8a also produced PE with almost narrow polydispersities (1.10–2.55) as is typical for single-site catalysts. However, PDI was broadened by time.     

CuI Immobilized on Tricationic Ionic Liquid Anchored on Functionalized Magnetic Hydrotalcite (Fe3O4/HT-TIL-CuI) as a Novel,Magnetic and Efficient Nanocatalyst for Ullmann-Type C–N Coupling Reaction

One of the most important reactions in organic synthesis is Ullmann-type C–N coupling reaction which has been used for preparation of numerous biologically active compounds. In this work, CuI immobilized on tricationic ionic liquid anchored on functionalized magnetic hydrotalcite (Fe₃O₄/HT-TIL-CuI) has been successfully prepared and fully characterized by different techniques, including fourier-transform infrared spectroscopy, vibrating sample magnetometer, thermo gravimetric analysis, transmission electron microscopy, field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy, elemental mapping, zeta potential, X-ray diffraction, temperature programmed desorption of ammonia (NH₃-TPD), temperature-programmed reduction and inductively coupled plasma. The results showed that the as-prepared nanocatalyst possesses plate-like morphology with approximate size of 50 nm and superparamagnetic behavior. Also, total acidity and total hydrogen consumption of the nanocatalyst were measured to be 8.5 and 1.41 mmol g^?1, respectively. This nanocatalyst exhibited favorable performance for C–N coupling reaction among a variety of aryl halides and N(H)-heterocycles (benzimidazoles, pyrazoles and triazoles) in the presence of 2.5 mol% of nanocatalyst without any additives under air atmosphere revealing high yields in all cases. Besides, it is noted that in the present system the desired product can be easily and quickly isolated and nanocatalyst also recovered magnetically from the reaction mixture employing a permanent magnet for at least six consecutive trials without a discernible decrease in catalytic activity which makes the proposed methodology appropriate for industrial. The findings demonstrated the advantages of the present method as no need for neutral atmosphere, appropriate times, recyclability of the catalyst, broad substrate scope, minimization of chemical waste, simple purification of products, easy workup process, and high yields.

     

Hybrid Paper–Plastic Microchip for Flexible and High‐Performance Point‐of‐Care Diagnostics

A low‐cost and easy‐to‐fabricate microchip remains a key challenge for the development of true point‐of‐care (POC) diagnostics. Cellulose paper and plastic are thin, light, flexible, and abundant raw materials, which make them excellent substrates for mass production of POC devices. Herein, a hybrid paper–plastic microchip (PPMC) is developed, which can be used for both single and multiplexed detection of different targets, providing flexibility in the design and fabrication of the microchip. The developed PPMC with printed electronics is evaluated for sensitive and reliable detection of a broad range of targets, such as liver and colon cancer protein biomarkers, intact Zika virus, and human papillomavirus nucleic acid amplicons. The presented approach allows a highly specific detection of the tested targets with detection limits as low as 10² ng mL^?1 for protein biomarkers, 10³ particle per milliliter for virus particles, and 10² copies per microliter for a target nucleic acid. This approach can potentially be considered for the development of inexpensive and stable POC microchip diagnostics and is suitable for the detection of a wide range of microbial infections and cancer biomarkers.     

Effectiveness of pressurised carbon dioxide for inactivation of Escherichia coli isolated from sewage sludge

This research explored the possible application of pressurised carbon dioxide (P CO(2)), a promising non-thermal sterilisation technique, for the treatment of sewage sludge (SS) before anaerobic digestion to inactivate pathogenic microorganisms. Escherichia coli was selected as the test organism and was isolated from SS and maintained in pure culture. The growth curve of the isolated strain was determined by measuring the optical density (OD) in liquid culture medium and relating this information to the spread plate count so that a culture of known cell density could be grown for optimisation experiments. Inactivation of E. coli was enhanced by increase in pressure (1,500, 2,000 and 2,800 kPa) and treatment time (from 0.75 to 24 h). A short exposure time at high pressure was sufficient to provide a degree of inactivation which could also be achieved by longer exposure at lower pressure. Complete inactivation (8 log(10) reduction) was possible at all three pressures. scanning (SEM) and transmission (TEM) electron microscopy studies of E. coli treated with P CO(2) revealed that the cell walls were ruptured, and the cytoplasm was unevenly distributed and had lost its density, indicating the possible leakage of intracellular substances.     

Poly(DL-lactide-co-ε-caprolactone) and poly(DL-lactide-co-glycolide) blends for biomedical application: Physical properties,cell compatibility,and in vitro degradation behavior

Poly(DL-lactide-co-ε-caprolactone) (PLCL) and poly(DL-lactide-co-glycolide) (PLGA) blends of various compositions were prepared. Fractured sections of PLCL/PLGA blends did not evidence phase separation and blend glass transition temperatures suggested some degree of blend compatibility. The elastic modulus showed a negative deviation from the additive law of mixture. Superior biocompatibility in terms of fibroblast NIH 3T3 cell adhesion and proliferation, better mechanical properties, and a more homogeneous phase were obtained with PLCL/PLGA 25/75 blend. Rapid degradation of PLCL phase (4–8 weeks) in PLCL/PLGA 25/75 blend led to a porous structure, which makes it a potential candidate for drug delivery systems.     

Black Nickel Coating and Color Anodized Layers for Solar Absorber

Solar selective absorbers are considered as an essential part of a thermal solar collector for which the optical properties are dependent upon their structure and surface morphology. In this paper, optical properties of Ni-pigmented anodized are compared with black electroless nickel coatings. The effect of heat treatment on optical properties of the coatings was also investigated. Anodized films were formed in 6 M phosphoric acid followed by a black coloration process. Scanning electron microscope was used to study the morphology, and X-ray diffraction was employed to identify the phases present. Evaluation of optical properties was carried out by spectral reflectance. Evaluation of the optical characteristics showed that Ni-pigmented anodized and black electroless samples, after heat treatment, had the highest absorption coefficient at about 0.98 as well as the lowest emission coefficient. The ξ factor reached about 6 in heat treated Ni-pigmented anodized layer and offered optimal properties in this research.