The Identification of Small Molecule Inhibitors That Reduce Invasion and Metastasis of Aggressive Cancers

Transformed epithelial cells can activate programs of epithelial plasticity and switch from a sessile, epithelial phenotype to a motile, mesenchymal phenotype. This process is linked to the acquisition of an invasive phenotype and the formation of distant metastases. The development of compounds that block the acquisition of an invasive phenotype or revert the invasive mesenchymal phenotype into a more differentiated epithelial phenotype represent a promising anticancer strategy. In a high-throughput assay based on E-cadherin (re)induction and the inhibition of tumor cell invasion, 44,475 low molecular weight (LMW) compounds were screened. The screening resulted in the identification of candidate compounds from the PROAM02 class. Selected LMW compounds activated E-cadherin promoter activity and inhibited cancer cell invasion in multiple metastatic human cancer cell lines. The intraperitoneal administration of selected LMW compounds reduced the tumor burden in human prostate and breast cancer in vivo mouse models. Moreover, selected LMW compounds decreased the intra-bone growth of xenografted human prostate cancer cells. This study describes the identification of the PROAM02 class of small molecules that can be exploited to reduce cancer cell invasion and metastases. Further clinical evaluation of selected candidate inhibitors is warranted to address their safety, bioavailability and antitumor efficacy in the management of patients with aggressive cancers.     

Thermal and dynamic mechanical behavior of poly(lactic acid) (PLA)-based electrospun scaffolds for tissue engineering

Electrospun scaffolds can find numerous applications, including biomedical; for example, tissue engineering. Poly-L-lactic acid is considered suitable for these applications, but its low-thermal stability and its poor mechanical properties limit this polymer use. The aim of this work is to obtain a modulation of the final scaffolds characteristics such as fibers dimension, wettability, elasticity, and resistance to rupture through the choice of the polymers to be electrospun. Different electrospun scaffolds containing gelatin, Poly-DL-lactic acid, different percentages of cellulose nanocrystals and an elastin peptide have been produced. Thermal stability, physical structure, and its mechanical behavior have been studied. Results suggest that the electrospun scaffolds show better thermal and mechanical properties than bulk materials; that is, the scaffolds with the best hydrophilic and thermomechanical properties are the samples containing 3% (wt/wt) of CNCs and elastin peptide.     

Efficacy of zinc salts to protect glass against atmospheric alteration. Part II: Possible passivation mechanisms

To investigate the origin of the protection effect of zinc salts against glass atmospheric alteration, the speciation of Zn²⁺ ions on glass according to the deposit protocol and the Zn²⁺ surface concentration, and its change over time, was investigated in the light of the respective performances of the treatments. In that respect, a combination of various characterization methods of the glass surface and near-surface was used before and after aging experiments (temperature, relative humidity (RH) control) of the Zn-treated glass. Different Zn-species could be observed on the surface of the treated glass: chemisorbed species, physisorbed species and precipitated hydroxide phases, their respective distribution being highly dependent on the nature of the treatment and on the Zn²⁺ surface concentration. GI-XAS (Zn K-edge) and ToF-SIMS experiments pointed out the conversion by thermal activation of these surface species into chemisorbed species inserted in the glass network in the near-surface. The chemisorbed species appear to be the most effective ones for the glass protection, possibly by making the surface less soluble, less hydrophilic and even by acting as a diffusion barrier.     

A level set-based structural optimization code using FEniCS

Structural and Multidisciplinary Optimization - This paper presents an educational code written using FEniCS, based on the level set method, to perform compliance minimization in structural...     

MoS2 dual-gate transistors with electrostatically doped contacts

Nano Research - Two-dimensional (2D) transition metal dichalcogenides (TMDs) such as molybdenum disulfide (MoS2) have been intensively investigated because of their exclusive physical properties...     

Affective decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in 10th-grade Chinese adolescent smokers

This study addressed the question of whether poor decision making would be associated with adolescent past 7-day smoking. We conducted a cross-sectional study of 208 10th-grade adolescents in Chengdu City, China. We used the Iowa Gambling Task (IGT) to assess decision-making, and the Self-ordered Pointing Task (SOPT) to assess working memory capacity. Paper and pencil questionnaires assessed the school academic performance (SAP) and smoking variables. The results showed that a significantly higher proportion of past 7-day smokers (91.7%) were susceptible to future smoking and cigarette offers from best friends compared to other levels of smokers (never, ever and past 30-day smokers). Consistent with these behavioral data, the neuropsychological assessments revealed that relative to never smokers, past 7-day adolescent smokers (but not ever smokers or past 30-day smokers) demonstrated significantly lower scores on the IGT. Moreover, a higher proportion of past 7-day smokers (91.7%) performed poorly (no more than an overall net score of 10) on the IGT than nonsmokers and irregular (ever or past 30-day) smokers (about 65.3%). There were no differences on working memory performance for smokers (at any level) compared to never smokers after adjusting for school-type. In addition, logistic regression showed that the IGT significantly predicted past 7-day smoking after controlling for the working memory, school academic performance and demographic variables. These results suggest that poor affective decision making might predispose some adolescents to smoking in the future or in the social situations where their peers are smoking. Intervention targeting affective decision making might hold promise for reducing adolescents' risks for substance use.     

Film extrusion of sunflower protein isolate

Film extrusion of sunflower protein isolate (SFPI) was studied. The influence of die temperature (85–160°C), water and glycerol contents were investigated through appearance, mechanical and thermomechanical properties, and swelling behavior in water of films. It was demonstrated that highest temperature, well above SFPI denaturation temperature in the compound, highest glycerol content (70 parts for 100 parts of SFPI), and medium water content (20 parts for 100 parts of SFPI) gave the most regular and smoothest film (as seen on SEM micrographs). Its ultimate tensile strength, Young's modulus, and strain at break were, respectively, 3.2 MPa, 17.7 MPa, and 73%. Soaked in water, its swelling was about 186% w/w but the film was quiet insoluble. Effect of temperature and plasticizer content were discussed in relation to the kinetic of SFPI denaturation. These first results are very promising for the development of biodegradable protein‐based films. POLYM. ENG. SCI. 46:1635–1640, 2006. © 2006 Society of Plastics Engineers.     

Assessing total and renewable energy in Brazilian automotive fuels. A life cycle inventory (LCI) approach

This article uses a first approach LCI procedure to evaluate total and renewable energy and CO₂ emissions in Brazilian automotive fuels life cycle (LC). The LC model is structured and modular, capable of being successively refined if necessary. The procedure is applied to passenger car use in urban traffic, comparing three fuels used in Brazil (gasoline with 25% ethanol, pure ethanol and compressed natural gas), considering their use in urban traffic in the city of Rio de Janeiro. An in deep research was made to collect representative and unpublished data of Brazilian automotive fuels LC reality, what is considered a main contribution. The results show where specific advantages occur, particularly in the use of renewable fuels made from biomass, an option already practiced and appropriate for Brazilian reality. The use of gasoline with 25% ethanol shows the lowest total energy consumption for the LC, with similar performance to that of compressed natural gas and 36% better than ethanol from sugarcane. However, the last alternative has the advantage of depending almost exclusively on renewable energy (93%) and producing less net CO₂ emissions.