2,529 research outputs found

    The Gates Of Gladness : On The Road To Sunshine Land

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    https://digitalcommons.library.umaine.edu/mmb-vp/1492/thumbnail.jp

    America Never Took Water : And America Never Will

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    https://digitalcommons.library.umaine.edu/mmb-vp/5251/thumbnail.jp

    Cell patterning on photolithographically defined parylene-C:SiO2 substrates

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    Cell patterning platforms support broad research goals, such as construction of predefined in vitro neuronal networks and the exploration of certain central aspects of cellular physiology. To easily combine cell patterning with Multi-Electrode Arrays (MEAs) and silicon-based ‘lab on a chip’ technologies, a microfabrication-compatible protocol is required. We describe a method that utilizes deposition of the polymer parylene-C on SiO(2 )wafers. Photolithography enables accurate and reliable patterning of parylene-C at micron-level resolution. Subsequent activation by immersion in fetal bovine serum (or another specific activation solution) results in a substrate in which cultured cells adhere to, or are repulsed by, parylene or SiO(2) regions respectively. This technique has allowed patterning of a broad range of cell types (including primary murine hippocampal cells, HEK 293 cell line, human neuron-like teratocarcinoma cell line, primary murine cerebellar granule cells, and primary human glioma-derived stem-like cells). Interestingly, however, the platform is not universal; reflecting the importance of cell-specific adhesion molecules. This cell patterning process is cost effective, reliable, and importantly can be incorporated into standard microfabrication (chip manufacturing) protocols, paving the way for integration of microelectronic technology

    Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites

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    The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.Work in the DJH laboratory is supported by the Medical Research Council under grant ML/L007266/1. All calculations were performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/) provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England, and were funded by the EPSRC under grants EP/F032773/1 and EP/J017639/1

    Developing a quality assurance metric: a panoptic view

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    This article is a post-print of the published article that may be accessed at the link below. Copyright @ 2006 Sage Publications.There are a variety of techniques that lecturers can use to get feedback on their teaching - for example, module feedback and coursework results. However, a question arises about how reliable and valid are the content that goes into these quality assurance metrics. The aim of this article is to present a new approach for collecting and analysing qualitative feedback from students that could be used as the first stage in developing more reliable quality assurance metrics. The approach, known as the multi-dimensional crystal view, is based on the belief that individuals have different views on the benefits that the embedded process in a system can have on the behaviour of the system. The results of this study indicate that in the context of evaluation and feedback methods, the multi-dimensional approach appears to provide the opportunity for developing more effective student feedback mechanisms

    Academic Major, Gender, Personal Values, And Reactions To An Ethical Dilemma

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    Recent corporate scandals have increased public interest in the area of business ethics.  This study examines the relationship of gender and choice of academic major to personal values and to ethical choices, and the relationship of personal values to ethical choices.  Two hundred fifty three subjects read a case that presented a tax evasion dilemma.  The subjects responded to a series of action statements related to the ethical dilemma and completed a personal values survey.  The responses to the action statements were used to calculate a tax compliance score.  Participants were also asked to make a choice as to whether the taxpayer should or should not report all of the taxable income.  The results indicate that both the tax compliance score and the tax payment choice differed by gender and academic major.  Furthermore, gender differences were found on five of the ten personal value constructs and academic major differences were found on four of the ten personal value constructs.  With regard to the relationship of personal values to ethical choices, it was found that three of the personal value constructs were correlated with the compliance score and the tax payment decision

    Can the United States Afford a “No-Fault” System of Compensation for Medical Injury?

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    One of the key issues separating US critics of a no-fault alternative to the tort system for compensating victims of medical injury from supporters is its anticipated cost. Results from a study are presented that estimate the costs of a no-fault system, one that is similar to the system now in operation in Sweden, within the context of the US health care system
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