Bright fluorescent dsDNA probes: novel polycationic asymmetric monomethine cyanine dyes based on thiazolopyridine‐quinolinium chromophore

Seven tri‐ and tetracationic monomeric and homodimeric monomethine cyanine dyes based on thiazolo[4,5‐b]pyridinium and quinolinium end groups were synthesised and characterised. The dyes were tested as fluorescent DNA intercalating probes to apply in DNA gel electrophoresis. The DNA samples stained with all dyes from the series demonstrated bright fluorescent signals. DNA fragments were successfully visualised under orange and green filters as well as under standard UV transillumination. Two of the studied dyes revealed higher sensitivity to DNA when compared with the commercial dimeric cyanine dye TOTO‐1. Their sensitivity reached that of the commercial dimeric cyanine dye YOYO‐1, but the emission was shifted to longer wavelengths. These qualities make the dyes suitable to apply in a wide range of medical and scientific analytical methods.     

Measuring technological diversification: identifying the effects of patent scale and patent scope

Although technological diversification is an important strategic decision for both large and small firms alike, the conventional method of measuring such diversification may well introduce significant scale bias against small- and medium-sized firms. We examine this issue in this study using a sample of 73 Taiwanese integrated-circuit (IC) design firms covering the period from 1995 to 2007 and conclude that the conventional measure of technological diversification reflects the spread or distribution amongst technology classes of a company’s current technology portfolio, and does not capture the incremental expansion in technological scope, or the ‘dynamic act of diversification’, as reflected in our alternative scope measure. Our results suggest clear constraints on the applications made under the conventional index, particularly for firms with small patent scale.     

Testing the reproducibility and robustness of the cancer biology literature by robot

Scientific results should not just be ‘repeatable’ (replicable in the same laboratory under identical conditions), but also ‘reproducible’ (replicable in other laboratories under similar conditions). Results should also, if possible, be ‘robust’ (replicable under a wide range of conditions). The reproducibility and robustness of only a small fraction of published biomedical results has been tested; furthermore, when reproducibility is tested, it is often not found. This situation is termed ‘the reproducibility crisis'', and it is one the most important issues facing biomedicine. This crisis would be solved if it were possible to automate reproducibility testing. Here, we describe the semi-automated testing for reproducibility and robustness of simple statements (propositions) about cancer cell biology automatically extracted from the literature. From 12 260 papers, we automatically extracted statements predicted to describe experimental results regarding a change of gene expression in response to drug treatment in breast cancer, from these we selected 74 statements of high biomedical interest. To test the reproducibility of these statements, two different teams used the laboratory automation system Eve and two breast cancer cell lines (MCF7 and MDA-MB-231). Statistically significant evidence for repeatability was found for 43 statements, and significant evidence for reproducibility/robustness in 22 statements. In two cases, the automation made serendipitous discoveries. The reproduced/robust knowledge provides significant insight into cancer. We conclude that semi-automated reproducibility testing is currently achievable, that it could be scaled up to generate a substantive source of reliable knowledge and that automation has the potential to mitigate the reproducibility crisis.     

Parental affect and coping.

Parental affect and coping strategies have been identified as being important for the understanding of the processes involved in the socialization of children. In the present study, 24 fathers (mean age 35.21 yrs old) and 62 mothers (mean age 35.05 yrs) (unrelated) described a stressful incident with one of their children and completed questionnaires addressing their appraisal of the event, their affect, and consequent coping strategy. Both child characteristics (age, birth order, and gender) and parent characteristics (gender, affect intensity, and ego level) were examined in relation to parents' appraisal of the cause of the event, their affect, and their coping strategy. Feelings of being angry, afraid, sad, and guilty, and use of coping strategies are discussed in light of the need for further research on emotion in parenting situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Harnessing the power of interpretive language.

Argues that the traditional Freudian-inspired picture of psychotherapy simplifies the psychotherapy process by failing to call attention to the connotative dimensions of language used in the therapy session. Psychological language is rich with connotation, and even though Freud's technical writings draw attention away from the connotative structures of language, his case reports reveal how important it was in his actual procedure. The author attempts to elucidate the neglected dimensions of connotation and to show how therapists can use a sensitive mastery of connotation to foster therapeutic growth. (6 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unliganded epidermal growth factor receptor dimerization induced by direct interaction of quinazolines with the ATP binding site

Receptor dimerization is critical for signaling by the epidermal growth factor receptor (EGFR) tyrosine kinase. This occurs after binding of the receptor's extracellular domain by ligand or bivalent antibodies. The role of other receptor domains in dimerization is less clear, and there are no examples of dimers induced by direct perturbation of the EGFR kinase domain. Submicromolar concentrations of AG-1478 and AG-1517, quinazolines specific for inhibition of the EGFR kinase, induced reversible receptor dimerization in vitro and in intact A431 cells. Consistent with the inhibitory effect of quinazolines on receptor kinase activity, the dimers formed lacked a detectable Tyr(P) signal. Quinazoline-induced EGFR dimerization was abrogated in vitro by ATP and the ATP analog adenyl-5'-yl imidodiphosphate. Receptors with a single-point mutation in the ATP binding site as well as wild-type EGFR with a covalent modification of the ATP site failed to dimerize in response to AG-1478 and AG-1517. These data suggest that EGFR dimerization can be induced by the interaction of quinazolines at the ATP site in the absence of receptor ligand binding. In SKBR-3 cells, the quinazolines induced the formation of inactive EGFR/ErbB-2 heterodimers, potentially sequestering ErbB-2 from interacting with other coreceptors of the ErbB family. Structural studies of the quinazoline interaction with the EGFR tyrosine kinase domain should allow for an analysis of receptor-specific chemical features required for binding to the ATP site and disruption of signaling, a strategy that can be perhaps applied to other tumor cell receptor systems.     

Applying a political model to program development

Politics encompasses personal behaviors that dominate much of day-to-day decision-making in organizations. Conflict arises when various groups with different goals, interests, values and perceptions attempt to influence policy or decision making to meet their own interests, needs, goals or values. In this paper, Baldridge's political model is used to analyze the conflict experienced in development of a hospital-based discharge planning program.     

Using Dihedral Angles for Edge Extraction in Range Data

The volume of raw range image data that is required to represent just a single scene can be extensive; hence direct interpretation of range images can incur a very high computational cost. Range image feature extraction has been identified as a mechanism to produce a more compact scene representation, in particular using features such as edges and surfaces, and hence enables less costly scene interpretation for applications such as object recognition and robot navigation. We present an approach to edge detection in range images that can be used directly with any range data, regardless of whether the data have regular or irregular spatial distribution. The approach is evaluated with respect to accuracy of both edge location and visual results are also provided.     

Polyester networks based upon epoxidized and maleinated natural oils

Novel families of flexible, semiflexible and rigid crosslinked polyesters were prepared from modified natural oils such as soybean, rape-seed and linseed oil. Maleinated oils were used as anhydride-functional curing agents of epoxy resins such as bisphenol-A-diglycidylether and epoxidized natural oils. A new class of unsaturated polyester resins was based upon maleic anhydride, epoxidized natural oils and styrene. The resulting thermosetting polyesters were reinforced with natural fibers such as hemp and flax fibers. The influence of molecular architectures, curing conditions and formulations on thermal, mechanical and morphological properties were investigated.