Phosphate Coordination to Metal-Organic Layer Secondary Building Units Prolongs Drug Retention for Synergistic Chemoradiotherapy

Chemoradiotherapy combines radiotherapy with concurrent chemotherapy to potentiate antitumor activity but exacerbates toxicities and causes debilitating side effects in cancer patients. Herein, we report the use of a nanoscale metal-organic layer (MOL) as a 2D nanoradiosensitizer and a reservoir for the slow release of chemotherapeutics to amplify the antitumor effects of radiotherapy. Coordination of phosphate-containing drugs to MOL secondary building units prolongs their intratumoral retention, allowing for continuous release of gemcitabine monophosphate (GMP) for effective localized chemotherapy. In the meantime, the MOL sensitizes cancer cells to X-ray irradiation and provides potent radiotherapeutic effects. GMP-loaded MOL (GMP/MOL) enhances cytotoxicity by 2-fold and improves radiotherapeutic effects over free GMP in vitro. In a colon cancer model, GMP/MOL retains GMP in tumors for more than four days and, when combined with low-dose radiotherapy, inhibits tumor growth by 98 %. The synergistic chemoradiotherapy enabled by GMP/MOL shows a cure rate of 50 %, improves survival, and ameliorates cancer-proliferation histological biomarkers.     

New indole alkaloid from Peschiera affinis (Apocynaceae)

A new indole alkaloid of the pyridocarbazole type, named 6N-hydroxy-olivacine, and two known compounds, 2N-oxide-olivacine and olivacine, were isolated from roots of Peschiera affinis. The structures of the compounds were determined by spectroscopic {IR and extensive NMR (COSY, HMQC, HMBCand NOESY)} and EIMS analysis.     

Comparative computational studies of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives as potential antinociceptive agents

In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a-i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series.     

Environmentally friendly sonocatalysis promoted preparation of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles

An efficient and green synthesis of thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles via the condensation of chalcones with thiosemicarbazide in ethanol and KOH under ultrasound irradiation is reported. The products were isolated in good yields after short reaction times.     

Comparing predator–prey models with hidden and explicit resources

In this paper two mathematical models are proposed and analyzed to elucidate the influence on a generalist predator of its hidden and explicit resources. Boundedness of the system’s trajectories, feasibility, local and global stability of the equilibria for both models are established, as well as possible local bifurcations. The findings indicate that the relevant behaviour of the system, including switching of stability, extinction and persistence of the involved populations, depends mainly on the reproduction rate of the favorite prey. To achieve full ecosystem survival some balance between the respective grazing pressures exerted by the predator on the prey populations needs to be maintained, while higher grazing pressure just on one species always leads to its extinction.     

A biased random-key genetic algorithm for road congestion minimization

One of the main goals in transportation planning is to achieve solutions for two classical problems, the traffic assignment and toll pricing problems. The traffic assignment problem aims to minimize total travel delay among all travelers. Based on data derived from the first problem, the toll pricing problem determines the set of tolls and corresponding tariffs that would collectively benefit all travelers and would lead to a user equilibrium solution. Obtaining high-quality solutions for this framework is a challenge for large networks. In this paper, we propose an approach to solve the two problems jointly, making use of a biased random-key genetic algorithm for the optimization of transportation network performance by strategically allocating tolls on some of the links of the road network. Since a transportation network may have thousands of intersections and hundreds of road segments, our algorithm takes advantage of mechanisms for speeding up shortest-path algorithms.     

Consistencies and inconsistencies in students' solutions to algebraic ‘single-value’ inequalities

This paper describes students’ solutions to a commonly taught and not commonly taught inequality. The findings showed students’ difficulties. Participants implicitly and explicitly exhibited two intuitive beliefs: inequalities must result in inequalities and solving inequalities and equations are the same process. Following the analysis of students’ written solutions, individual interviews were conducted that gave a better insight into their reasoning and provided some ideas for teaching. The concluding section of the paper offers relevant educational implications.     

Bayesian Copulae Distributions, with Application to Operational Risk Management

The aim of this paper is to introduce a new methodology for operational risk management, based on Bayesian copulae. One of the main problems related to operational risk management is understanding the complex dependence structure of the associated variables. In order to model this structure in a flexible way, we construct a method based on copulae. This allows us to split the joint multivariate probability distribution of a random vector of losses into individual components characterized by univariate marginals. Thus, copula functions embody all the information about the correlation between variables and provide a useful technique for modelling the dependency of a high number of marginals. Another important problem in operational risk modelling is the lack of loss data. This suggests the use of Bayesian models, computed via simulation methods and, in particular, Markov chain Monte Carlo. We propose a new methodology for modelling operational risk and for estimating the required capital. This methodology combines the use of copulae and Bayesian models.