Nano-SAR Modeling for Predicting the Cytotoxicity of Metal Oxide Nanoparticles to PaCa2.

Nowadays, the impact of engineered nanoparticles (NPs) on human health and environment has aroused widespread attention. It is essential to assess and predict the biological activity, toxicity, and physicochemical properties of NPs. Computation-based methods have been developed to be efficient alternatives for understanding the negative effects of nanoparticles on the environment and human health. Here, a classification-based structure-activity relationship model for nanoparticles (nano-SAR) was developed to predict the cellular uptake of 109 functionalized magneto-fluorescent nanoparticles to pancreatic cancer cells (PaCa2). The norm index descriptors were employed for describing the structure characteristics of the involved nanoparticles. The Random forest algorithm (RF), combining with the Recursive Feature Elimination (RFE) was employed to develop the nano-SAR model. The resulted model showed satisfactory statistical performance, with the accuracy (ACC) of the test set and the training set of 0.950 and 0.966, respectively, demonstrating that the model had satisfactory classification effect. The model was rigorously verified and further extensively compared with models in the literature. The proposed model could be reasonably expected to predict the cellular uptakes of nanoparticles and provide some guidance for the design and manufacture of safer nanomaterials.

Evaluating genotoxicity of metal oxide nanoparticles: Application of advanced supervised and unsupervised machine learning techniques.

Presence of missing data points in datasets is among main challenges in handling the toxicological data for nanomaterials. As the processing of missing data is an important part of data analysis, we have introduced a read-across approach that uses a combination of supervised and unsupervised machine learning techniques to fill the missing values. A series of classification models (supervised learning) was developed to predict class label, and self-organizing map approach (unsupervised learning) was used to estimate relative distances between nanoparticles and refine results obtained during supervised learning. In this study, genotoxicity of 49 silicon and metal oxide nanoparticles in Ames and Comet tests. Collected literature data did not demonstrate significant variations related to the change of size including selected bulk materials. Genotoxicity-related features of nanomaterials were represented by ionic characteristics. General tendencies found in the current study were convincingly linked to known theories of genotoxic action at nano-level. Mechanisms of primary and secondary genotoxic effects were discussed in the context of developed models.

Combinatorial search for iron/titanium-based ternary oxides with a visible-light response.

A combinatorial approach has been carried out to systematically investigate visible-light responsiveness of Fe-Ti-M (M: various metal elements) oxides for photoelectrochemical water splitting. Among the 25 elements tested, strontium was the most effective. A ternary metal oxide with the composition Fe(86.1)Ti(9.6)Sr(4.3)O(x) has been identified as a new lead structure for a visible-light responsive, n-type semiconductor. We have conducted various kinds of characterization of the Fe-Ti-Sr oxide semiconductor and discussed the reason why Sr in the Fe-Ti oxide gave the highest photocurrent.

Microbiological characterisation of southern African medicinal and cosmetic clays.

The effects of traditionally used medicinal and cosmetic clays in southern Africa on selected microorganisms were studied using microbiological media. The clay pH, microchemical composition, kind of associated microorganisms and antimicrobial activity of clays against test microorganisms were determined. The clays contained varying numbers of microorganisms which ranged from 0 up to 105 CFU/g. Clay pH ranged from 2.3-8.9. Neither Escherichia coli, nor other faecal coliforms were detected. Clays of pH value of <4 displayed antimicrobial activities. Clays which were active against test microorganisms had Na(2)O, Al(2)O(3), SiO(2), SO(3), CuO or Cl(2)O as major components. Microbial activity of clays was attributed mainly to low pH but cations such as Cu, Al, S or Cl and various anions might have contributed to the microbicidal effects. No antimicrobial activity was established for many of the clays commonly used in the treatment of common ailments of microbial origin.

Antitumor studies. Part 1: design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents.

Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, andKB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC(50) and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK.

Development of a basic procedure to design sorption processes.

The intention of this work is to offer, within the shortest time, an appropriate sorption separation process for almost any odour problem. The development is based on the preparation and characterisation of new adsorbents, the strategy for the selection of the best adsorbent, the process engineering and the choice of a suitable regeneration procedure. In this context a new method for the characterisation of the adsorbents - the adsorption profile analysis - was developed. The classification of the adsorbents was carried out by means of a cluster analysis, which simplifies the selection of the most suitable adsorbent for a particular problem. The physical and chemical behaviour of silica-adsorbents could be tailored by silanisation of the surfaces. Methods for the determination of process engineering parameters were developed, established and used. Adsorption kinetics and isotherms were determined with a magnetic adsorption balance. In a laboratory-scale fixed bed adsorber, breakthrough curves of different support materials were investigated and compared. For the investigations of different regeneration procedures, four innovative methods were employed: microwave desorption, ultrasonic desorption, ultrasonic-water desorption and extraction with water. Of the four desorption methods examined, microwave desorption and ultrasonic-water desorption demonstrated the best results.

Two case studies of highly insoluble plutonium inhalation with implications for bioassay.

Two well characterised Pu inhalation cases show some remarkable similarities between substantially different types of Pu oxide. The circumstances of exposure, therapy, bioassay data, chemical solubility studies and dosimetry associated with these cases suggest that highly insoluble Pu may be more common than previously thought, and can pose significant challenges to bioassay programmes.

In vivo measurement of Pu dissolution parameters of MOX aerosols and related uncertainties in the values of the dose per unit intake.

The aim of this study was to compare dissolution parameter values for Pu from industrial MOX with different Pu contents. For this purpose, preliminary results obtained after inhalation exposure of rats to MOX containing 2.5% Pu are reported and compared to those obtained previously with MOX containing 5% Pu. Dissolution parameter values appear to increase when the amount of Pu decreases. Rapid fractions, f(r), of 4 x 10(-3) (s.d. = 2 x 10(-3)) and 1 x 10(-3) (s.d. = 6 x 10(-4)) and slow dissolution rates, s(s) of 2 x 10(-4) d(-1) (standard deviation, sigma = 5 x 10(-5)) and 5 x 10(-5) d(-1) (sigma = 1 x 10(-5)) were derived for MOX containing 2.5 and 5% of Pu, respectively. Simulations were performed to assess uncertainties on dose due to experimental errors. The relative standard deviations of the dose per unit intake (DPUI) due to f(r) (4-8%), are far less than those due to s(s) (about 20%), which is the main parameter altering the dose. Although quite different dissolution parameter values were derived, similar DPUIs were obtained for MOX aerosols containing 2.5 and 5% Pu which appear close to that for default Type S values.

Characterisation and dissolution of depleted uranium aerosols produced during impacts of kinetic energy penetrators against a tank.

Aerosols produced during impacts of depleted uranium (DU) penetrators against the glacis (sloping armour) and the turret of a tank were sampled. The concentration and size distribution were determined. Activity median aerodynamic diameters were 1 microm (geometric standard deviation, sigma(g) = 3.7) and 2 microm (sigma(g) = 2.5), respectively, for glacis and turret. The mean air concentration was 120 Bq m(-3), i.e. 8.5 mg m(-3) of DU. Filters analysed by scanning electron microscopy (SEM) and X ray diffraction showed two types of particles (fine particles and large molten particles) composed mainly of a mixture of uranium and aluminium. The uranium oxides were mostly U3O8, UO2.25 and probably UO3.01 and a mixed compound of U and Al. The kinetics of dissolution in three media (HCO3-, HCl and Gamble's solution) were determined using in-vitro tests. The slow dissolution rates were respectively slow, and intermediate between slow and moderate, and the rapid dissolution fractions were mostly intermediate between moderate and fast. According to the in-vitro results for Gamble's solution, and based on a hypothetical single acute inhalation of 90 Bq, effective doses integrated up to 1 y after incorporation were 0.54 and 0.56 mSv, respectively, for aerosols from glacis and turret. In comparison, the ICRP limits are 20 mSv y(-1) for workers and 1 mSv y(-1) for members of the public. A kidney concentration of approximately 0.1 microg U g(-1) was predicted and should not, in this case, lead to kidney damage.

Measuring aerosols generated inside armoured vehicles perforated by depleted uranium ammunition.

In response to questions raised after the Gulf War about the health significance of exposure to depleted uranium (DU), the US Department of Defense initiated a study designed to provide an improved scientific basis for assessment of possible health effects on soldiers in vehicles struck by these munitions. As part of this study, a series of DU penetrators were fired at an Abrams tank and a Bradley fighting vehicle, and the aerosols generated by vehicle perforation were collected and characterised. A robust sampling system was designed to collect aerosols in this difficult environment and monitor continuously the sampler flow rates. The aerosol samplers selected for these tests included filter cassettes, cascade impactors, a five-stage cyclone and a moving filter. Sampler redundancy was an integral part of the sampling system to offset losses from fragment damage. Wipe surveys and deposition trays collected removable deposited particulate matter. Interior aerosols were analysed for uranium concentration and particle size distribution as a function of time. They were also analysed for uranium oxide phases, particle morphology and dissolution in vitro. These data, currently under independent peer review, will provide input for future prospective and retrospective dose and health risk assessments of inhaled or ingested DU aerosols. This paper briefly discusses the target vehicles, firing trajectories, aerosol samplers and instrumentation control systems, and the types of analyses conducted on the samples.