p53 in polyoma virus transformed REF52 cells

While cellular transformation by small DNA tumour viruses usually involves targeting the product of the p53 tumour suppressor gene by a virally encoded protein, none of the three polyoma virus (Py) specified T antigens have been observed to interact with p53. We show that primary mouse embryo fibroblasts and REF52 cells, which resemble primary cells in requiring co-operating oncogenes for transformation, cannot be transformed by the Py oncogene, middle T-antigen (PyMT), alone. These cells can be transformed by the complete Py early region, which encodes the Py large, middle and small T-antigens. We find that PyMT can transform rodent cells lacking a functional p53 protein (p53 null mouse embryo fibroblasts and DN-REF52 cells which contain a dominant negative p53). In Py transformed REF52 cells (Py-REF52) there is no significant accumulation of p53 protein, as opposed to SV40 transformed REF52 cells (SV-REF52) in which the amount of steady state p53 protein is elevated. However accumulation of p53 is observed following exposure of Py-REF52 cells to u.v. Treatment of Py-REF52 cells with X-rays results in a rapid increase in the levels of the p53-induced proteins p21/WAF1 and MDM2. In untransformed REF52 cells, X-irradiation causes p53 activation, which results in induction of both G1/S and G2/M blocks. In SV-REF52 and DN-REF52 cells, p53 abrogation results in the absence of both the G1/S and G2/M blocks. Only the absence of a G1/S block is observed in Py-REF52 cells exposed to X-irradiation. Together these results indicate that in contrast to most other DNA tumour viruses, Py does not appear to interfere with the DNA damage induced transactivation activities of the p53 protein but absence of a functional p53 protein can mediate transformation by the PyMT oncogene in the absence of other co-operating oncogenes. Possible modes of transformation by Py are discussed.     

Performance analysis of Drever-Hall laser frequency stabilizationusing a proportional+integral servo

In this paper, we derive analytical expressions for finite gain, finite bandwidth laser frequency locking systems. The common case of Drever-Hall (FM sideband) locking to a Fabry-Perot cavity is discussed, using a proportional+integral (PI) controller as an example. The effects of nonnegligible loop time-delay on stability are discussed, and an optimal design procedure for a frequency locking system is given     

Dyadic perfectionism as a predictor of relationship continuity and distress among college students.

This study examined the nature and impact of dyadic perfectionism over a 3-month interval within a sample of 116 college students who were currently involved in an intimate heterosexual relationship. Dyadic perfectionism scores were stable and correlated as expected with scores on concurrent measures of adult attachment orientations and relationship satisfaction. Logistic regression analyses revealed that, controlling for initial commitment status and adult attachment orientations, Time 1 dyadic perfectionism scores significantly and uniquely predicted relationship continuity 3 months later. Lastly, controlling for social desirability, relationship commitment status, and Time 1 adult attachment orientation scores, Time 1 dyadic perfectionism scores also uniquely predicted Time 2 relationship distress. Findings provide additional evidence that dyadic perfectionism is a risk factor for relationship dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intergranular films at Au-sapphire interfaces

The existence of nanometer-thick amorphous equilibrium films at metal-ceramic interfaces has been experimentally verified for the Au–Al₂O₃ system. The films were formed using a novel experimental approach, in which thin sputtered films of Au were dewetted on a sapphire substrate which was previously partially wetted with drops of anorthite glass (CaO–2SiO₂–Al₂O₃). High-resolution transmission electron microscopy and qualitative analytical transmission electron microscopy were used to confirm the existence of the amorphous films. In addition, positive and relatively large Hamaker constants were calculated for the Au-film-Al₂O₃ interface, which indicates the existence of an attractive van der Waals force which stabilizes the film, similar to equilibrium films at grain boundaries in ceramics. A ∼ 1 nm thick surface film was also detected on the (0001) surface of sapphire substrates partially wetted by anorthite glass. The refractive index required to stabilize the surface films, via a positive Hamaker constant, is explored.     

N-(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability

The MT₂-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT₁ and MT₂ binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation.     

Key factors that influence the UX of a dual-player game for the cognitive stimulation and motor rehabilitation of older adults

Universal Access in the Information Society - In this work, the results of usability and user experience (UX) evaluation of a serious video game for the cognitive stimulation and motor...     

Expanding the Toolbox of R-Selective Amine Transaminases by Identification and Characterization of New Members

Amine transaminases (ATAs) are used to synthesize enantiomerically pure amines, which are building blocks for pharmaceuticals and agrochemicals. R-selective ATAs belong to the fold type IV PLP-dependent enzymes, and different sequence-, structure- and substrate scope-based features have been identified in the past decade. However, our knowledge is still restricted due to the limited number of characterized (R)-ATAs, with additional bias towards fungal origin. We aimed to expand the toolbox of (R)-ATAs and contribute to the understanding of this enzyme subfamily. We identified and characterized four new (R)-ATAs. The ATA from Exophiala sideris contains a motif characteristic for d -ATAs, which was previously believed to be a disqualifying factor for (R)-ATA activity. The crystal structure of the ATA from Shinella is the first from a Gram-negative bacterium. The ATAs from Pseudonocardia acaciae and Tetrasphaera japonica are the first characterized (R)-ATAs with a shortened/missing N-terminal helix. The active-site charges vary significantly between the new and known ATAs, correlating with their diverging substrate scope.     

Usability perception of different video game devices in elderly users

The purpose of this study was to evaluate the usability perception of seniors on video game use with different control devices. Twenty-four seniors participated in the study (12 women, 12 men, 69 years old in average) and eight children (8 years old in average). The setting included the use of two Kinect motion sensors, three computers, three projectors, three video cameras, two audio devices, the Angry Birds and Happy Sky videogames, one Xbox 360 console, a Nintendo Wii device and a Touchscreen configured so that participants could play the games in senior–child pairs. Data were collected according to user friendliness, experience and social interaction. This study suggests that video game control devices for seniors should be adapted to compensate for their function, sensor and cognitive limitations.     

An approach to textile dye removal using sawdust from Aspidosperma polyneuron

The textile industry is responsible for discarding wastewater contaminated with dyes. The timber industry generates waste in the form of sawdust. The aim of the present study was to evaluate the adsorptive potential of sawdust obtained from the Aspidosperma polyneuron tree for the removal of the textile dye from wastewater. Sawdust was subjected to different pre-treatments (acid, alkaline and polyethyleneimine) in order to increase its adsorption capacity. Based on the results from the isotherms, treatment with polyethyleneimine (PEI) led to the greatest adsorption capacity and fits the Freundlich model, indicating cooperative adsorption. Other treatments with sawdust best fit the Langmuir model, but the untreated sawdust presented better results than the treated sawdust. These results were only surpassed by sawdust treated with PEI. A. polyneuron revealed good potential for use as an adsorbent to remove dyes, which is a novel result, since to date there is no study on its use as a sorbent material.