Kinetic modeling and exploratory numerical simulation of chloroplastic starch degradation

<p>Abstract</p> <p>Background</p> <p>Higher plants and algae are able to fix atmospheric carbon dioxide through photosynthesis and store this fixed carbon in large quantities as starch, which can be hydrolyzed into sugars serving as feedstock for fermentation to biofuels and precursors. Rational engineering of carbon flow in plant cells requires a greater understanding of how starch breakdown fluxes respond to variations in enzyme concentrations, kinetic parameters, and metabolite concentrations. We have therefore developed and simulated a detailed kinetic ordinary differential equation model of the degradation pathways for starch synthesized in plants and green algae, which to our knowledge is the most complete such model reported to date.</p> <p>Results</p> <p>Simulation with 9 internal metabolites and 8 external metabolites, the concentrations of the latter fixed at reasonable biochemical values, leads to a single reference solution showing β-amylase activity to be the rate-limiting step in carbon flow from starch degradation. Additionally, the response coefficients for stromal glucose to the glucose transporter k_catand K_Mare substantial, whereas those for cytosolic glucose are not, consistent with a kinetic bottleneck due to transport. Response coefficient norms show stromal maltopentaose and cytosolic glucosylated arabinogalactan to be the most and least globally sensitive metabolites, respectively, and β-amylase k_catand K_Mfor starch to be the kinetic parameters with the largest aggregate effect on metabolite concentrations as a whole. The latter kinetic parameters, together with those for glucose transport, have the greatest effect on stromal glucose, which is a precursor for biofuel synthetic pathways. Exploration of the steady-state solution space with respect to concentrations of 6 external metabolites and 8 dynamic metabolite concentrations show that stromal metabolism is strongly coupled to starch levels, and that transport between compartments serves to lower coupling between metabolic subsystems in different compartments.</p> <p>Conclusions</p> <p>We find that in the reference steady state, starch cleavage is the most significant determinant of carbon flux, with turnover of oligosaccharides playing a secondary role. Independence of stationary point with respect to initial dynamic variable values confirms a unique stationary point in the phase space of dynamically varying concentrations of the model network. Stromal maltooligosaccharide metabolism was highly coupled to the available starch concentration. From the most highly converged trajectories, distances between unique fixed points of phase spaces show that cytosolic maltose levels depend on the total concentrations of arabinogalactan and glucose present in the cytosol. In addition, cellular compartmentalization serves to dampen much, but not all, of the effects of one subnetwork on another, such that kinetic modeling of single compartments would likely capture most dynamics that are fast on the timescale of the transport reactions.</p

Additional Dimensions to the Study of Funnels in Combinatorial Landscapes

The global structure of travelling salesman's fitness landscapes has recently revealed the presence of multiple `funnels'. This implies that local optima are organised into several clusters, so that a particular local optimum largely belongs to a particular funnel. Such a global structure can increase search difficulty, especially, when the global optimum is located in a deep, narrow funnel. Our study brings more precision (and dimensions) to the notion of funnels with a data-driven approach using Local Optima Networks and the Chained Lin-Kernighan heuristic. We start by exploring the funnel 'floors', characterising them using the notion of communities from complex networks. We then analyse the more complex funnel 'basins'. Since their depth is relevant to search, we visualise them in 3D. Our study, across a set of TSP instances, reveals a multi-funnel structure in most of them. However, the specific topology varies across instances and relates to search difficulty. Finally, including a stronger perturbation into Chained Lin-Kernighan proved to smooth the funnel structure, reducing the number of funnels and enlarging the valley leading to global optima

Neuroanatomical Study of Periprostatic Nerve Distributions Using Human Cadaver Prostate

We investigated the distribution and navigation of periprostatic nerve fibers and constructed a 3-dimensional model of nerve distribution. A total of 5 cadaver specimens were serially sectioned in a transverse direction with 0.5 cm intervals. Hematoxylineosin staining and immunohistochemical staining were then performed on whole-mount sections. Three representative slides from the base, mid-part, and apex of each prostate were subsequently divided into 4 sectors: two lateral, one ventral, and one dorsal (rectal) part. The number of nerve fibers, the distance from nerve fiber to prostate capsule, and the nerve fiber diameters were analyzed on each sector from the representative slides by microscopy. Periprostatic nerve fibers revealed a relatively even distribution in both lateral and dorsal parts of the prostate. There was no difference in the distances from the prostate capsule to nerve fibers. Nerve fibers in the ventral area were also thinner as compared to other areas. In conclusion, periprostatic nerve fibers were observed to be distributed evenly in the periprostatic area, with the exception of the ventral area. As the number of nerve fibers on the ventral part is fewer in comparison, an excessive high up incision is insignificant during the nerve-sparing radical prostatectomy

Magnetically modified TiO2 powders - microstructure and magnetic properties

AbstractThe anatase (TiO2) particles magnetically modified by iron oxides and prepared by an innovating technological procedure are studied from the viewpoint of microstructure and a complex analysis of magnetic behaviour at room and elevated temperatures. Scanning electron microscopy observations have yielded variable shapes of particles in the composite powder whereas the iron oxide particles of diameter bellow 1μm were detected on the surface of the TiO2. The dominant magnetite (Fe3O4) accompanied by a small amount of maghemite (γ-Fe2O3) and/or hematite (α- Fe2O3) were analysed by X-ray powder diffraction. A relatively high saturation magnetization (3.38 Am2/kg), negative dipolar interactions, and the low values of reversible and irreversible part of magnetic susceptibility were found out from magnetic measurements at room temperature. During a thermomagnetic treatment the composite sample has been going through a few magnetic phase transitions and transforms into a fully paramagnetic state around 850K. After its cooling to the room temperature an undesirable magnetic hardening of the sample has occurred

Understanding Phase Transitions with Local Optima Networks: Number Partitioning as a Case Study

Phase transitions play an important role in understanding search difficulty in combinatorial optimisation. However, previous attempts have not revealed a clear link between fitness landscape properties and the phase transition. We explore whether the global landscape structure of the number partitioning problem changes with the phase transition. Using the local optima network model, we analyse a number of instances before, during, and after the phase transition. We compute relevant network and neutrality metrics; and importantly, identify and visualise the funnel structure with an approach (monotonic sequences) inspired by theoretical chemistry. While most metrics remain oblivious to the phase transition, our results reveal that the funnel structure clearly changes. Easy instances feature a single or a small number of dominant funnels leading to global optima; hard instances have a large number of suboptimal funnels attracting the search. Our study brings new insights and tools to the study of phase transitions in combinatorial optimisation

Official Discrepancies: Kosovo Independence and Western European Rhetoric

This article examines approaches and official discrepancies characterising Western European rhetoric with regard to the Kosovo status question. Since the early 1980s, Kosovo has been increasingly present in European debates, culminating with the 1999 international intervention in the region and subsequent talks about its final status. Although the Kosovo Albanians proclaimed independence in February 2008 and the majority of EU Member States decided to recognise Kosovo as an independent state, Western European rhetoric has been rather divided. This article shows that in addition to five EU members who have decided not to recognise Kosovo from the very beginning, and thus are powerful enough to affect its further progress, both locally and internationally, some of the recognisers, although having abandoned the policy of ‘standards before status’, have also struggled to develop full support for the province – a discrepancy that surely questions the overall Western support for Kosovo’s independence

European Union Approaches to Human Rights Violations in Kosovo before and after Independence

This article examines European Union (EU) approaches to the question of human rights violations in Kosovo before and after its proclamation of independence, in February 2008. While the 1999 NATO-led humanitarian intervention in the region was often justified as necessary due to the continuous abuses of human rights, perpetrated by the Serbian forces against the ethic Kosovo Albanians, the post-interventionist period has witnessed a dramatic reversal of roles, with the rights of the remaining Serbian minority being regularly abused by the dominant Albanian population. However, in contrast to the former scenario, the Brussels administration has remained quite salient about the post-independence context – a grey zone of unviable political and social components, capable of generating new confrontations and human rights abuses within the borders of Kosovo. Aware of this dynamic and the existing EU official rhetoric, it is possible to conclude that the embedded human rights concerns in Kosovo are not likely to disappear, but even more importantly, their relevance has been significantly eroded