Sensitivity analysis and experimental design of a stiff signal transduction pathway model

Sensitivity analysis is normally used to analyze how sensitive a system is with respect to the change of parameters or initial conditions and is perhaps best known in systems biology via the formalism of metabolic control analysis [1, 2]. The nuclear factor B (NF-B) signalling pathway is an important cellular signalling pathway, of which protein phosphorylation is a major factor controlling the activation of further downstream events. The NF-κB proteins regulate numerous genes that play important roles in inter- and intra-cellular signalling, cellular stress responses, cell growth, survival, and apoptosis. As such, its specificity and its role in the temporal control of gene expression are of crucial physiological interest

Relationships between speech perception, phonological awareness and language in the development of literacy

It is widely accepted that literacy development is associated with phonological awareness, speech perception and language skills. The extent to which speech perception and language contribute to literacy, directly or indirectly via phonological awareness, is however unclear. This study aimed to achieve a more holistic understanding by investigating the contribution of all variables to literacy, simultaneously. Consistent with the Comprehensive Language Approach, it was hypothesised that, along with language and phonological awareness, speech perception would also contribute uniquely to literacy, and that mutually-reinforcing relationships between all variables would be found, such that the pattern of contributions to literacy from all variables would differ as a function of literacy skill. A task battery assessing speech perception, language, phonological awareness and literacy was administered to a sample of fifty-four 6-year old children. Multiple regression analyses revealed only phonological awareness and speech perception to contribute uniquely to the full range of literacy scores, explaining 8% and 20% of the variance respectively. A mean split of literacy scores was used to compute upper and lower halves of the range. No significant contributions were found to either shared or unique variability in the upper half of the literacy range, likely due to restricted sensitivity in measures. In the lower half of the literacy range, unique contributions to literacy were found only for speech perception and language. Results appear to reflect greater stability in the relationship between speech perception and literacy than in relationships between language and literacy and phonological awareness and literacy, where level of literacy skill and experience may be implicated. Clinical implications for instruction and remediation are discussed, as is the need for further research to determine whether mutually-reinforcing relationships may assume different patterns, associated with different developmental stages

Computer recommendations for an automatic approach and landing system for V/STOL aircraft. Volume 1 - Computer recommendations

Evaluation of digital computer for V/STOL aircraft automatic approach and landing syste

CWRML: representing crop wild relative conservation and use data in XML

Background Crop wild relatives are wild species that are closely related to crops. They are valuable as potential gene donors for crop improvement and may help to ensure food security for the future. However, they are becoming increasingly threatened in the wild and are inadequately conserved, both in situ and ex situ. Information about the conservation status and utilisation potential of crop wild relatives is diverse and dispersed, and no single agreed standard exists for representing such information; yet, this information is vital to ensure these species are effectively conserved and utilised. The European Community-funded project, European Crop Wild Relative Diversity Assessment and Conservation Forum, determined the minimum information requirements for the conservation and utilisation of crop wild relatives and created the Crop Wild Relative Information System, incorporating an eXtensible Markup Language (XML) schema to aid data sharing and exchange. Results Crop Wild Relative Markup Language (CWRML) was developed to represent the data necessary for crop wild relative conservation and ensure that they can be effectively utilised for crop improvement. The schema partitions data into taxon-, site-, and population-specific elements, to allow for integration with other more general conservation biology schemata which may emerge as accepted standards in the future. These elements are composed of sub-elements, which are structured in order to facilitate the use of the schema in a variety of crop wild relative conservation and use contexts. Pre-existing standards for data representation in conservation biology were reviewed and incorporated into the schema as restrictions on element data contents, where appropriate. Conclusion CWRML provides a flexible data communication format for representing in situ and ex situ conservation status of individual taxa as well as their utilisation potential. The development of the schema highlights a number of instances where additional standards-development may be valuable, particularly with regard to the representation of population-specific data and utilisation potential. As crop wild relatives are intrinsically no different to other wild plant species there is potential for the inclusion of CWRML data elements in the emerging standards for representation of biodiversity data

Computer recommendations for an automatic approach and landing system for V/STOL aircraft. Volume 2 - Equations

Automatic approach and landing system for V/STOL aircraf

On the Conflicting Estimations of Pigment Site Energies in Photosynthetic Complexes: A Case Study of the CP47 Complex

Citation: Reinot, T., Chen, J. H., Kell, A., Jassas, M., Robben, K. C., Zazubovich, V., & Jankowiak, R. (2016). On the Conflicting Estimations of Pigment Site Energies in Photosynthetic Complexes: A Case Study of the CP47 Complex. Analytical Chemistry Insights, 11, 35-48. doi:10.4137/aci.s32151We focus on problems with elucidation of site energies (E-0(n)) for photosynthetic complexes (PSCs) in order to raise some genuine concern regarding the conflicting estimations propagating in the literature. As an example, we provide a stern assessment of the site energies extracted from fits to optical spectra of the widely studied CP47 antenna complex of photosystem II from spinach, though many general comments apply to other PSCs as well. Correct values of E-0(n) for chlorophyll (Chl) a in CP47 are essential for understanding its excitonic structure, population dynamics, and excitation energy pathway(s). To demonstrate this, we present a case study where simultaneous fits of multiple spectra (absorption, emission, circular dichroism, and nonresonant hole-burned spectra) show that several sets of parameters can fit the spectra very well. Importantly, we show that variable emission maxima (690-695 nm) and sample-dependent bleaching in nonresonant hole-burning spectra reported in literature could be explained, assuming that many previously studied CP47 samples were a mixture of intact and destabilized proteins. It appears that the destabilized subpopulation of CP47 complexes could feature a weakened hydrogen bond between the 13(1)-keto group of Chl29 and the PsbH protein subunit, though other possibilities cannot be entirely excluded, as discussed in this work. Possible implications of our findings are briefly discussed

Representation of Markov chains by random maps: existence and regularity conditions

We systematically investigate the problem of representing Markov chains by families of random maps, and which regularity of these maps can be achieved depending on the properties of the probability measures. Our key idea is to use techniques from optimal transport to select optimal such maps. Optimal transport theory also tells us how convexity properties of the supports of the measures translate into regularity properties of the maps via Legendre transforms. Thus, from this scheme, we cannot only deduce the representation by measurable random maps, but we can also obtain conditions for the representation by continuous random maps. Finally, we present conditions for the representation of Markov chain by random diffeomorphisms.Comment: 22 pages, several changes from the previous version including extended discussion of many detail

Long-Term Treatment with Extended-Release Carbidopa– Levodopa (IPX066) in Early and Advanced Parkinson’s Disease: A 9-Month Open-Label Extension Trial

Background and Objective IPX066 is a multiparticulate extended-release formulation of carbidopa–levodopa, designed to produce prolonged therapeutic levodopa plasma concentrations. This 9-month open-label extension study assessed its long-term safety and clinical utility in early and advanced Parkinson’s disease (PD). Methods Participants were enrolled from two phase III IPX066 studies and one open-label phase II study. Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies. Adjustment was allowed throughout the extension. Clinical utility measures included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings. Results Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced patients were taking IPX066 three or four times daily (median: 1450 mg/day). Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa–levodopa, the median dosages correspond to *500 and *1015 mg/day of IR levodopa in early and advanced PD, respectively. Based on the plasma profiles previously observed in PD patients, the IPX066 regimens in the extension can be estimated to provide a levodopa Cmax (maximum plasma drug concentration) similar to or lower than that provided by IR regimens during the antecedent trials. UPDRS and PGI findings showed sustained treatment effects throughout the extension. Conclusion During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy