Elementary units of cortical activity? The rise and fall of the cortical column

The roots of the concept of cortical columns stretch far back into the history of neuroscience. The impulse to compartmentalise the cortex into functional units can be seen at work in the phrenology of the beginning of the nineteenth century. At the beginning of the next century Korbinian Brodmann and several others published treatises on cortical architectonics. Later, in the middle of that century, Lorente de No writes of chains of ‘reverberatory’ neurons orthogonal to the pial surface of the cortex and called them ‘elementary units of cortical activity’. This is the first hint that a columnar organisation might exist. With the advent of microelectrode recording first Vernon Mountcastle (1957) and then David Hubel and Torsten Wiesel provided evidence consistent with the idea that columns might constitute units of physiological activity. This idea was backed up in the 1970s by clever histochemical techniques and culminated in Hubel and Wiesel’s well-known ‘ice-cube’ model of the cortex and Szentogathai’s brilliant iconography. The cortical column can thus be seen as the terminus ad quem of several great lines of neuroscientific research: currents originating in phrenology and passing through cytoarchitectonics; currents originating in neurocytology and passing through Lorente de No. Famously, Huxley noted the tragedy of a beautiful hypothesis destroyed by an ugly fact. Famously, too, human visual perception is orientated toward seeing edges and demarcations when, perhaps, they are not there. Recently the concept of cortical columns has come in for the same radical criticism that undermined the architectonics of the early part of the twentieth century. Does history repeat itself? This paper reviews this history and asks the question.

21-residue peptide's dynamics at and between elementary structural transitions

Elementary conformational changes of the backbone of a 21-residue peptide A5(A3RA)3A are studied using molecular dynamics simulations in explicit water. The processes of the conformational transitions and the regimes of stationary fluctuations between them are investigated using minimal perturbations of the system. The perturbations consist of a few degrees rotation of the velocity of one of the systems' atoms and keep the system on the same energy surface. It is found that (i) the system dynamics is insignificantly changed by the perturbations in the regimes between the transitions; (ii) it is very sensitive to the perturbations just before the transitions that prevents the peptide from making the transitions; and (iii) the perturbation of any atom of the system, including distant water molecules is equally effective in preventing the transition. The latter implies strongly collective dynamics of the peptide and water during the transitions.

Design and evaluation of compound metformin/glipizide elementary osmotic pump tablets

A simple elementary osmotic pump (EOP) system that could deliver metformin hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time was developed in order to reduce the problems associated with multidrug therapy of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to pharmacists to provide satisfactory extended release of MT and GZ. In this paper sodium carbonate was used to modulate the solubility of GZ within the core and MT was not only one of the active ingredients but also the osmotic agent. The optimal EOP was found to deliver both drugs at a rate of approximately zero order for up to 10 h in pH 6.8, independent of environment media. In-vivo evaluation was performed relative to the equivalent dose of conventional MT tablet and GZ tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect in comparison with the conventional product. The prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.

Time for action? Elementary engineering education - Challenging teachers, policy makers and parents

Grounded in the findings of a three year exploratory student whereby teachers' and policy makers' perceptions of elementary level engineering education were analysed, this paper focuses upon three strands of engineering education activity: Pedagogy: Practice, and: Policy. Taking into account the challenges associated with introducing engineering education at an elementary level across the UK, the paper critiques the role played by the 'competition model' in promoting engineering to children and 4 to 11 years. In considering the 'added value' that appropriately developed engineering education activities can offer in the classroom the discussion argues that elementary level engineering has the potential to reach across the curriculum, offering context and depth in many different areas. The paper concludes by arguing that by introducing the discipline to children at a foundational level, switching on their 'Engineering Imaginations' and getting them to experience the value and excitement of engineering, maths and applied science a new "Educational Frontier" will be forged. © American Society for Engineering Education, 2014.