Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity

Genotoxicity of commercial colloidal and laboratory-synthesized silica nanoparticles was tested using the single cell gel electrophoresis or Comet assay. By using a carefully developed protocol and careful characterization of the nanoparticle dispersions, Comet assays were performed on 3T3-L1 fibroblasts with 3, 6, and 24 h incubations and 4 or 40 microg/ml of silica nanoparticles. No significant genotoxicity was observed for the nanoparticles tested under the conditions described, and results were independently validated in two separate laboratories, showing that in vitro toxicity testing can be quantitatively reproducible.     

Improved in vitro anti-tumoral activity, intracellular uptake and apoptotic induction of gemcitabine-loaded pegylated unilamellar liposomes

Anaplastic thyroid carcinoma is one of the most aggressive and lethal solid carcinomas affecting humans. A major limit of the chemotherapeutic agents is represented by their low therapeutic index. In this work, we investigated the possibility of improving the anti-tumoral activity of gemcitabine by using pegylated unilamellar liposomes. Liposomes were made up of 1,2-dipalmitoyl-sn-glycero-3-phospocholine monohydrate/cholesterol/N-(carbonyl-methoxypolyethylene glycol-2000)-1, 2-distearoyl-sn-glycero-3-phosphoethanolamine (6:3:1 molar ratio) and they were prepared with a pH gradient to improve the gemcitabine loading capacity. The anti-tumoral efficacy of the liposomal formulation was tested in vitro on human anaplastic thyroid carcinoma cells (ARO) in culture, comparing the effects with those of the free drug. Gemcitabine-loaded unilamellar liposomes had a mean size approximately 200 nm with a zeta potential approximately -2 mV. The liposomal carrier noticeably improved the anti-tumoral activity of gemcitabine against ARO cells in terms of both dose-dependent cytotoxic effect and of drug exposition effect. Namely, gemcitabine-loaded liposomes showed a cytotoxic effect (58.2% increase of cell mortality at 1 microM with respect to free drug) after 12 h incubation, while the free drug showed a significant activity only after 72 h incubation. Moreover, a significant effect on the cell mortality appeared at 0.1 microM and 100% mortality was detected at a concentration of 1 microM of gemcitabine-loaded liposomes, while the free drug elicited the same effect at a concentration of 100 microM. The improved anti-tumoral activity of gemcitabine determined by the liposomal carrier was due to a greater intracellular uptake. The intracellular gemcitabine levels as a function of time showed a sinusoidal profile with peaks after 2 h, 6 h and 11 h, related to the cellular cycle of ARO. PARP cleavage and DNA fragmentation analysis provided clear evidence of the apoptosis induction in ARO cells by treatment with liposomally entrapped gemcitabine after 72 h incubation. Thus, gemcitabine-loaded liposomes may have a potential therapeutic relevance for the treatment of anaplastic thyroid carcinoma.     

Inclusions,Stress Concentrations and Surface Condition in Bending Fatigue of an H13 Tool Steel

Combined effects of inclusions, surface condition and geometrical stress concentration on the fatigue strength of a tool steel have been studied. Bending fatigue testing was performed for milled tool components and smooth specimens produced from an experimental AISI H13 tool steel with varying additions of sulphur and oxygen. Inclusion distributions of the different test series were determined. Fracture surfaces after fatigue failures were studied in a scanning electron microscope. The sulphur content does not have a significant influence on the fatigue strength of the milled tool components in the range of 0.02 ‐ 0.09 wt%. A clear reduction in the fatigue strength is obtained for the smooth specimens when the steel becomes rich in inclusions. Here, the oxide type inclusions dominated as crack initiators and the effect of sulphides was smaller. The results demonstrate the reduced effect of inclusions on the fatigue strength in components with large stress concentrations and rough surfaces.     

Anhedonia as a phenotype for the Val1??Met COMT polymorphism in relatives of patients with schizophrenia.

The Val1??Met polymorphism of the catechol-O-methyltransferase (COMT) gene has been associated with aspects of schizophrenia that are possibly related to the disorder's pathogenesis. The present study investigated the Val1??Met polymorphism in relation to anhedonia--a construct central to negative schizotypy. Anhedonia and other schizotypal characteristics were assessed in relatives of patients with schizophrenia, relatives of patients with bipolar disorder, and nonpsychiatric controls using the Chapman schizotypy scales and the Schizotypal Personality Questionnaire. Compared with controls, relatives of individuals with schizophrenia had elevated scores on Chapman scales for social anhedonia and physical anhedonia, while relatives of patients with bipolar disorder exhibited only increased scores on the Social Anhedonia Scale. As a group, relatives of patients with schizophrenia who were homozygous for the val allele of the COMT polymorphism showed the highest elevations in self-reported social and physical anhedonia. Associations with the COMT polymorphism were absent in relatives of patients with bipolar disorder and control participants. Findings suggest that anhedonia is manifest in individuals who carry genetic liability for schizophrenia and is associated with the Val1??Met polymorphism of the COMT gene. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasticity of executive functioning in young and older adults: Immediate training gains, transfer, and long-term maintenance.

The authors investigated immediate training gains, transfer effects, and 18-month maintenance after 5 weeks of computer-based training in updating of information in working memory in young and older subjects. Trained young and older adults improved significantly more than controls on the criterion task (letter memory), and these gains were maintained 18 months later. Transfer effects were in general limited and restricted to the young participants, who showed transfer to an untrained task that required updating (3-back). The findings demonstrate substantial and durable plasticity of executive functioning across adulthood and old age, although there appear to be age-related constraints in the ability to generalize the acquired updating skill. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A controlled trial of psychodynamic psychotherapy for co-occurring borderline personality disorder and alcohol use disorder.

A randomized controlled trial was conducted to determine whether a manual-based psychodynamic treatment, labeled dynamic deconstructive psychotherapy (DDP), would be feasible and effective for individuals with co-occurring borderline personality disorder (BPD) and alcohol use disorder. Thirty participants were assessed every 3 months during a year of treatment with either DDP or treatment as usual (TAU) in the community. DDP participants showed statistically significant improvement in parasuicide behavior, alcohol misuse, institutional care, depression, dissociation, and core symptoms of BPD, and treatment retention was 67% to 73%. Although TAU participants received higher average treatment intensity, they showed only limited change during the same period. The results support the feasibility, tolerability, and efficacy of DDP for the co-occurring subgroup and highlight the need for further research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sociodemographic associations with mental health and residential care utilization among juvenile delinquents.

Research has supported the notion that ethnoracial minorities in the juvenile justice system use fewer mental health services than Caucasians do. The authors' aim was to examine potential sociodemographic (including racial background) associations with the use of mental health and residential care among juvenile delinquents adjudicated through court services. The authors extracted demographic, mental health, and residential care data from archival records of 149 juveniles consecutively adjudicated from a midwestern city's juvenile court services facility (from 1999 to 2002). The authors found no significant associations with mental health treatment or residential care utilization based on ethnoracial background, age, gender, and educational level, neither in bivariate nor multivariate analyses. Implications for policy in the juvenile justice system are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Positioning of an isothermal heat storage layer in a building wall exposed to the external environment

The paper presents an idea for the enhancement of a building's thermal insulation component by adding into the structure a thin layer of a phase-change material (PCM). The proposed solution can be dedicated, for example, to an external partition of lightweight construction. The capacity for latent heat storage allowed it to stabilize the temperature inside the insulation layer in a daily cycle and to minimize the temperature difference between the internal and external surfaces. In this paper, different positions of a PCM layer in the thermal insulation of an external wall were analysed. The main goal of this work was to find the best position of the PCM layer, taking into account the indoor temperature and the meteorological conditions. The authors propose two parameters: the amount of stored energy and the dynamism of the charging/discharging processes. Taking into account large temperature fluctuations on the external surface during summer and winter, it was concluded that, for this specific case, the most appropriate solution would be an external position of the PCM with a melting temperature of 20°C.     

A Roadmap for Controlled and Efficient n‐Type Doping of Self‐Assisted GaAs Nanowires Grown by Molecular Beam Epitaxy

N‐type doping of GaAs nanowires has proven to be difficult because the amphoteric character of silicon impurities is enhanced by the nanowire growth mechanism and growth conditions. The controllable growth of n‐type GaAs nanowires with carrier density as high as 10²⁰ electron cm^?3 by self‐assisted molecular beam epitaxy using Te donors is demonstrated here. Carrier density and electron mobility of highly doped nanowires are extracted through a combination of transport measurement and Kelvin probe force microscopy analysis in single‐wire field‐effect devices. Low‐temperature photoluminescence is used to characterize the Te‐doped nanowires over several orders of magnitude of the impurity concentration. The combined use of those techniques allows the precise definition of the growth conditions required for effective Te incorporation.     

Instrumentation for medium-throughput two-dimensional capillary electrophoresis with laser-induced fluorescence detection

In two-dimensional capillary electrophoresis, a sample undergoes separation in the first dimension capillary by sieving electrophoresis. Fractions are periodically transferred across an interface into a second dimension capillary, where components are further resolved by micellar electrokinetic capillary electrophoresis. Previous instruments employed one pair of capillaries to analyze a single sample. We now report a multiplexed system that allows separation of five samples in parallel. Samples are injected into five first-dimension capillaries, fractions are transferred across an interface to 5 second-dimension capillaries, and analyte is detected by laser-induced fluorescence in a five-capillary sheath-flow cuvette. The instrument produces detection limits of 940 +/- 350 yoctomoles for 3-(2-furoyl)quinoline-2-carboxaldehyde labeled trypsin inhibitor in one-dimensional separation; detection limits degrade by a factor of 3.8 for two-dimensional separations. Two-dimensional capillary electrophoresis expression fingerprints were obtained from homogenates prepared from a lung cancer (A549) cell line, on the basis of capillary sieving electrophoresis (CSE) and micellar electrophoresis capillary chromatography (MECC). An average of 131 spots is resolved with signal-to-noise greater than 10. A Gaussian surface was fit to a set of 20 spots in each electropherogram. The mean spot width, expressed as standard deviation of the Gaussian function, was 2.3 +/- 0.7 transfers in the CSE dimension and 0.46 +/- 0.25 s in the MECC dimension. The standard deviation in spot position was 1.8 +/- 1.2 transfers in the CSE dimension and 0.88 +/- 0.55 s in the MECC dimension. Spot capacity was 300.