An improved multi-parametric programming algorithm for flux balance analysis of metabolic networks

Flux balance analysis has proven an effective tool for analyzing metabolic networks. In flux balance analysis, reaction rates and optimal pathways are ascertained by solving a linear program, in which the growth rate is maximized subject to mass-balance constraints. A variety of cell functions in response to environmental stimuli can be quantified using flux balance analysis by parameterizing the linear program with respect to extracellular conditions. However, for most large, genome-scale metabolic networks of practical interest, the resulting parametric problem has multiple and highly degenerate optimal solutions, which are computationally challenging to handle. An improved multi-parametric programming algorithm based on active-set methods is introduced in this paper to overcome these computational difficulties. Degeneracy and multiplicity are handled, respectively, by introducing generalized inverses and auxiliary objective functions into the formulation of the optimality conditions. These improvements are especially effective for metabolic networks because their stoichiometry matrices are generally sparse; thus, fast and efficient algorithms from sparse linear algebra can be leveraged to compute generalized inverses and null-space bases. We illustrate the application of our algorithm to flux balance analysis of metabolic networks by studying a reduced metabolic model of Corynebacterium glutamicum and a genome-scale model of Escherichia coli. We then demonstrate how the critical regions resulting from these studies can be associated with optimal metabolic modes and discuss the physical relevance of optimal pathways arising from various auxiliary objective functions. Achieving more than five-fold improvement in computational speed over existing multi-parametric programming tools, the proposed algorithm proves promising in handling genome-scale metabolic models.Comment: Accepted in J. Optim. Theory Appl. First draft was submitted on August 4th, 201

Pressure forces on sediment particles in turbulent open-channel flow : a laboratory study

Acknowledgements This research was sponsored by EPSRC grant EP/G056404/1 and their financial support is greatly appreciated. We also acknowledge Dr S. Cameron, who developed the PIV system and its algorithms. The design and construction of pressure sensors was carried out at the workshop and the experiments were conducted in the fluids laboratory at the University of Aberdeen. We therefore express our gratitude to the workshop and laboratory technicians and also to Mr M. Witz and Mr S. Gretland for their assistance in carrying out these experiments. The authors would also like to thank Professor J. Frohlich, Professor M. Uhlmann, Dr C.-B. Clemens and Mr B. Vowinckel for their useful suggestions and discussions throughout the course of this project. The Associate Editor Professor I. Marusic and four anonymous reviewers provided many useful and insightful comments and suggestions that have been gratefully incorporated into the final version.Peer reviewedPublisher PD

Aggressive Kaposi's Sarcoma in a 6-month-old African infant: Case Report and Review of the Literature.

Kaposi's sarcoma (KS), known to exist in Africa for a century now, was rare in children and unknown in the newborn. With the onset of the HIV/AIDS epidemic, a more aggressive, disseminated type of KS (AKS) was recognized. Recently KS was diagnosed in a 6-month-old infant in Tanzania. Data support the notion that HHSV8 infectivity can be potentiated with HIV infection and thus produce multiple lesions in different anatomical sites early in life. Furthermore, the available evidence would suggest a nonsexual route of HHSV8 infection, possibly from mother to fetus

The point of departure of a particle sliding on a curved surface

A particle is thrown tangentially on a surface. It is shown that for some surfaces and for special initial velocities the thrown particle leaves immediately the surface, and for special conditions it never leaves the surface. The conditions for leaving the surface is investigated. The problem is studied for a surface with the cross section $y=f(x)$. The surfaces with the equations $f(x)= -\alpha x^{k}\ (\alpha, k>0)$ is considered in more detail. At the end the effect of friction is also considered.Comment: 10 pages, 4 figure

Variation in the Thyrotropic Activity of Human Chorionic Gonadotropin in Chinese Hamster Ovary Cells Arises from Differential Expression of the Human Thyrotropin Receptor and Microheterogeneity of the Hormone.

The role of hCG as a stimulator of the human thyroid has been a subject of controversy, because discrepant results have been obtained in different in vitro assays. In an attempt to explain the variation observed in the thyroid response to hCG, we investigated the ability of hCG and that of its isoforms and glycosylation variants to inhibit [125I]bovine (b) TSH binding and stimulate adenylate cyclase in two clones, JP09 and JP26, of Chinese hamster ovary cells stably transfected with the human TSH receptor (hTSHr). The two clones differed with respect to the number of hTSHr expressed per cell (34,000 in JP09 and 2,000 in JP26 cells). Both responded extremely well to bTSH; the cAMP response to 0.001 IU/L bTSH was distinguishable from basal values. Interestingly, JP09 cells were readily stimulated by hCG (20-100 mg/L; 0.52-2.6 x 10(-6) mol/L) to release cAMP, whereas JP26 cells showed little if any response. Also, cAMP stimulation produced by asialo-hCG was 12-fold in JP09 cells and only 4-fold in JP26 cells compared to 45- and 67-fold stimulations by bTSH, respectively. Stimulation by asialo-hCG was approximately 30% that of bTSH in JP09 cells, but less than 6% in JP26 cells. When assessing the thyrotropic activity of the microheterogeneous isoforms of hCG, more alkaline pI forms were found to be more active than those of a more acidic pI regardless of whether they were derived from normal or molar pregnancy urine. Further studies with hCG, asialo-hCG, asialoagalacto-hCG, and deglycosylated hCG revealed that removal of sialic acid caused a marked increase in both its affinity for hTSHr and its cAMP-releasing potency, whereas removal of further carbohydrate, although it slightly enhanced receptor binding, was detrimental to adenylate cyclase activation. In conclusion, differences in hTSHr expression may cause a variation in the cAMP response to hCG or its glycosylation variants, as does the microheterogeneity of the hormone itself. These mechanisms may be responsible at least in part for the divergent responses of different cell types to hCG and render interpretation of the physiological meaning of the data obtained in recombinant receptor systems difficult