An ocean modelling and assimilation guide to using GOCE geoid products

We review the procedures and challenges that must be considered when using geoid data derived from the Gravity and steady-state Ocean Circulation Explorer (GOCE) mission in order to constrain the circulation and water mass representation in an ocean 5 general circulation model. It covers the combination of the geoid information with timemean sea level information derived from satellite altimeter data, to construct a mean dynamic topography (MDT), and considers how this complements the time-varying sea level anomaly, also available from the satellite altimeter. We particularly consider the compatibility of these different fields in their spatial scale content, their temporal rep10 resentation, and in their error covariances. These considerations are very important when the resulting data are to be used to estimate ocean circulation and its corresponding errors. We describe the further steps needed for assimilating the resulting dynamic topography information into an ocean circulation model using three different operational fore15 casting and data assimilation systems. We look at methods used for assimilating altimeter anomaly data in the absence of a suitable geoid, and then discuss different approaches which have been tried for assimilating the additional geoid information. We review the problems that have been encountered and the lessons learned in order the help future users. Finally we present some results from the use of GRACE geoid in20 formation in the operational oceanography community and discuss the future potential gains that may be obtained from a new GOCE geoid.

Identification of micro-scale anthropogenic CO2, heat and moisture sources – processing eddy covariance fluxes for a dense urban environment

Anthropogenic emissions of heat and exhaust gases play an important role in the atmospheric boundary layer, altering air quality, greenhouse gas concentrations and the transport of heat and moisture at various scales. This is particularly evident in urban areas where emission sources are integrated in the highly heterogeneous urban canopy layer and directly linked to human activities which exhibit significant temporal variability. It is common practice to use eddy covariance observations to estimate turbulent surface fluxes of latent heat, sensible heat and carbon dioxide, which can be attributed to a local scale source area. This study provides a method to assess the influence of micro-scale anthropogenic emissions on heat, moisture and carbon dioxide exchange in a highly urbanized environment for two sites in central London, UK. A new algorithm for the Identification of Micro-scale Anthropogenic Sources (IMAS) is presented, with two aims. Firstly, IMAS filters out the influence of micro-scale emissions and allows for the analysis of the turbulent fluxes representative of the local scale source area. Secondly, it is used to give a first order estimate of anthropogenic heat flux and carbon dioxide flux representative of the building scale. The algorithm is evaluated using directional and temporal analysis. The algorithm is then used at a second site which was not incorporated in its development. The spatial and temporal local scale patterns, as well as micro-scale fluxes, appear physically reasonable and can be incorporated in the analysis of long-term eddy covariance measurements at the sites in central London. In addition to the new IMAS-technique, further steps in quality control and quality assurance used for the flux processing are presented. The methods and results have implications for urban flux measurements in dense urbanised settings with significant sources of heat and greenhouse gases.

Crystal structures of Λ-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes

The ruthenium complex [Ru(phen)2(dppz)] (where phen is a phenanthroline and dppz a dipyridyl–phenazine ligand) is known as a ‘light switch’ complex because its luminescence in solution is significantly enhanced in the presence of DNA. This property is poised to serve in diagnostic and therapeutic applications, but its binding mode with DNA needs to be elucidated further. Here, we describe the crystal structures of the L enantiomer bound to two oligonucleotide duplexes. The dppz ligand intercalates symmetrically and perpendicularly from the minor groove of the d(CCGGTACCGG)2 duplex at the central TA/TA step, but not at the central AT/AT step of d(CCGGATCCGG)2. In both structures, however, a second ruthenium complex links the duplexes through the combination of a shallower angled intercalation into the C1C2/G9G10 step at the end of the duplex, and semi-intercalation into the G3G4 step of an adjacent duplex. The TA/TA specificity of the perpendicular intercalation arises from the packing of phenanthroline ligands against the adenosine residue.

First steps in experimental cancer evolution

Evolutionary processes play a central role in the development, progression and response to treatment of cancers. The current challenge facing researchers is to harness evolutionary theory to further our understanding of the clinical progression of cancers. Central to this endeavour will be the development of experimental systems and approaches by which theories of cancer evolution can be effectively tested. We argue here that the experimental evolution approach – whereby evolution is observed in real time and which has typically employed microorganisms – can be usefully applied to cancer. This approach allows us to disentangle the ecological causes of natural selection, identify the genetic basis of evolutionary changes and determine their repeatability. Cell cultures used in cancer research share many of the desirable traits that make microorganisms ideal for studying evolution. As such, experimental cancer evolution is feasible and likely to give great insight into the selective pressures driving the evolution of clinically destructive cancer traits. We highlight three areas of evolutionary theory with importance to cancer biology that are amenable to experimental evolution: drug resistance, social evolution and resource competition. Understanding the diversity, persistence and evolution of cancers is vital for treatment and drug development, and an experimental evolution approach could provide strategic directions and focus for future research.

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation.

One step forward, and two steps back: women and career progression in academia during times of uncertainty

While there is an extensive and still growing body of literature on women in academia and the challenges they encounter in career progression, there is little research on their experience specifically within a business school setting. In this study, we attempt to address this gap and examine the experiences and career development of female academics in a business school and how these are impacted by downsizing programmes. To this end, an exploratory case study is conducted. The findings of this study show that female business school academics experience numerous challenges in terms of promotion and development, networking, and the multiple and conflicting demands placed upon them. As a result, the lack of visibility seems to be a pertinent issue in terms of their career progression. Our data also demonstrates that that, paradoxically, during periods of downsizing women become more visible and thus vulnerable to layoffs as a consequence of the challenges and pressures created in their environment during this process. In this paper, we argue that this heightened visibility, and being subject to possible layoffs, further reproduces inequality regimes in academia.

Further characterization of muscarinic agonist-induced epileptiform bursting activity in immature rat piriform cortex, in vitro

The characteristics of muscarinic acetylcholine receptor agonist-induced epileptiform bursting seen in immature rat piriform cortex slices in vitro were further investigated using intracellular recording, with particular focus on its postnatal age-dependence (P+14-P+30), pharmacology, site(s) of origin and the likely contribution of the muscarinic acetylcholine receptor agonist-induced post-stimulus slow afterdepolarization and gap junction functionality toward its generation. The muscarinic agonist, oxotremorine-M (10 microM), induced rhythmic bursting only in immature piriform cortex slices; however, paroxysmal depolarizing shift amplitude, burst duration and burst incidence were inversely related to postnatal age. No significant age-dependent changes in neuronal membrane properties or postsynaptic muscarinic responsiveness accounted for this decline. Burst incidence was higher when recorded in anterior and posterior regions of the immature piriform cortex. In adult and immature neurones, oxotremorine-M effects were abolished by M1-, but not M2-muscarinic acetylcholine receptor-selective antagonists. Rostrocaudal lesions, between piriform cortex layers I and II, or layer III and endopiriform nucleus in adult or immature slices did not influence oxotremorine-M effects; however, the slow afterdepolarization in adult (but not immature) lesioned slices was abolished. Gap junction blockers (carbenoxolone or octanol) disrupted muscarinic bursting and diminished the slow afterdepolarization in immature slices, suggesting that gap junction connectivity was important for bursting. Our data show that neural networks within layers II-III function as primary oscillatory circuits for burst initiation in immature rat piriform cortex during persistent muscarinic receptor activation. Furthermore, we propose that muscarinic slow afterdepolarization induction and gap junction communication could contribute towards the increased epileptiform susceptibility of this brain area.

Auditory memory and the irrelevant sound effect: further evidence for changing state disruption

Four experiments investigate the hypothesis that irrelevant sound interferes with serial recall of auditory items in the same fashion as with visually presented items. In Experiment 1 an acoustically changing sequence of 30 irrelevant utterances was more disruptive than 30 repetitions of the same utterance (the changing-state effect; Jones, Madden, & Miles, 1992) whether the to-be-remembered items were visually or auditorily presented. Experiment 2 showed that two different utterances spoken once (a heterogeneous compound suffix; LeCompte & Watkins, 1995) produced less disruption to serial recall than 15 repetitions of the same sequence. Disruption thus depends on the number of sounds in the irrelevant sequence. In Experiments 3a and 3b the number of different sounds, the "token-set" size (Tremblay & Jones, 1998), in an irrelevant sequence also influenced the magnitude of disruption in both irrelevant sound and compound suffix conditions. The results support the view that the disruption of memory for auditory items, like memory for visually presented items, is dependent on the number of different irrelevant sounds presented and the size of the set from which these sounds are taken. Theoretical implications are discussed.