Algorithms for 13C metabolic flux analysis

The metabolism of an organism consists of a network of biochemical reactions that transform small molecules, or metabolites, into others in order to produce energy and building blocks for essential macromolecules. The goal of metabolic flux analysis is to uncover the rates, or the fluxes, of those biochemical reactions. In a steady state, the sum of the fluxes that produce an internal metabolite is equal to the sum of the fluxes that consume the same molecule. Thus the steady state imposes linear balance constraints to the fluxes. In general, the balance constraints imposed by the steady state are not sufficient to uncover all the fluxes of a metabolic network. The fluxes through cycles and alternative pathways between the same source and target metabolites remain unknown. More information about the fluxes can be obtained from isotopic labelling experiments, where a cell population is fed with labelled nutrients, such as glucose that contains 13C atoms. Labels are then transferred by biochemical reactions to other metabolites. The relative abundances of different labelling patterns in internal metabolites depend on the fluxes of pathways producing them. Thus, the relative abundances of different labelling patterns contain information about the fluxes that cannot be uncovered from the balance constraints derived from the steady state. The field of research that estimates the fluxes utilizing the measured constraints to the relative abundances of different labelling patterns induced by 13C labelled nutrients is called 13C metabolic flux analysis. There exist two approaches of 13C metabolic flux analysis. In the optimization approach, a non-linear optimization task, where candidate fluxes are iteratively generated until they fit to the measured abundances of different labelling patterns, is constructed. In the direct approach, linear balance constraints given by the steady state are augmented with linear constraints derived from the abundances of different labelling patterns of metabolites. Thus, mathematically involved non-linear optimization methods that can get stuck to the local optima can be avoided. On the other hand, the direct approach may require more measurement data than the optimization approach to obtain the same flux information. Furthermore, the optimization framework can easily be applied regardless of the labelling measurement technology and with all network topologies. In this thesis we present a formal computational framework for direct 13C metabolic flux analysis. The aim of our study is to construct as many linear constraints to the fluxes from the 13C labelling measurements using only computational methods that avoid non-linear techniques and are independent from the type of measurement data, the labelling of external nutrients and the topology of the metabolic network. The presented framework is the first representative of the direct approach for 13C metabolic flux analysis that is free from restricting assumptions made about these parameters.In our framework, measurement data is first propagated from the measured metabolites to other metabolites. The propagation is facilitated by the flow analysis of metabolite fragments in the network. Then new linear constraints to the fluxes are derived from the propagated data by applying the techniques of linear algebra.Based on the results of the fragment flow analysis, we also present an experiment planning method that selects sets of metabolites whose relative abundances of different labelling patterns are most useful for 13C metabolic flux analysis. Furthermore, we give computational tools to process raw 13C labelling data produced by tandem mass spectrometry to a form suitable for 13C metabolic flux analysis.

Fine root dry matter relative to mango (Mangifera indica) tree scion size grafted on size-controlling rootstocks, is negatively related to scion growth rate

Knowledge of root dry matter (DM) allocation, in relation to differing vigour conferred by rootstock cultivars, is required to understand the structural relationships between rootstock and scion. We investigated the mass of roots (four size classes up to 23 mm diameter) by coring proximal to five polyembryonic mango rootstock cultivars known to differ in their effects on the vigour and productivity of scion cultivar ‘Kensington Pride’, in a field trial of 13-year-old trees. Significant differences in fine (<0.64 and 0.64–1.88 mm diameter) and small (1.88–7.50 mm) root DM contents were observed between rootstock cultivars. There was a complex relationship between the amount of feeder (fine and small size classes) roots and scion size (trunk cross sectional area, TCSA), with intermediate size trees on rootstock MYP having the most feeder roots, while the smallest trees, on the rootstock Vellaikulamban had the least of these roots. Across rootstock cultivars, tree vigour (TCSA growth rate) was negatively and significantly related to the ratio of fine root DM/scion TCSA, suggesting this may be a useful indicator of the vigour that different rootstocks confer on the scion. In contrast non-ratio root DM and scion TCSA results had no significant relationships. The significant rootstock effects on orchard root growth and tree size could not be predicted from earlier differences in nursery seedling vigour, nor did seedling vigour predict root DM allocation.

Relative sensitivity of the corpus luteum of different days of pregnancy to LH-deprivation in the rat and hamster

Deprivation of endogenous LH by LH antiserum (LH A/S) in 6-day pregnant rats did not affect the luteal or serum progesterone within 24 h. LH A/S treatment on day 7 or 8 of pregnancy, however, caused a 70 and 92% reduction in luteal progesterone, respectively, within 24 h. Serum levels of progesterone showed a similar reduction. In the case of pregnant hamster, unlike the rat, there was a significant decrease in progesterone in the serum, luteal and non-luteal compartments whether the A/S was administered on day 4, 5 or 6. There was more than a 10-fold increase in the luteal cholesterol esters within 24 h whether the A/S was given on day 6, 7 or 8 of pregnancy in the rat. Rat corpora lutea of days 6 and 8 of pregnancy reacted in a like manner to LH-deprivation, showing an increased utilization of [U-14C]glucose to form 14CO2 in vitro. In the rat, LH (25 μg NIH-S19) administration in vivo either on day 6 or day 8 of pregnancy, caused within 2 h an increase in serum and non-luteal progesterone, but luteal progesterone was unchanged. On the other hand, LH administration to hamsters on day 8 of pregnancy caused an increase in progesterone levels in serum, luteal and non-luteal tissue. Incubation of corpora lutea isolated from untreated 6- and 8-day pregnant rats with LH brought about an increase in progesterone secretion into the medium in both cases. The results show that, even though LH-deprivation does not apparently affect progesterone concentration in the corpus luteum of 6-day pregnant rats, it does affect other metabolic parameters such as glucose utilization and cholesterol turnover, suggesting that the corpus luteum of early pregnancy exhibits a continuous dependency on LH for the maintainence of metabolic functions.

Studies on the relative biopotencies and intestinal absorption of different apo-beta-carotenoids in rats and chickens.

1. The biopotencies relative to beta-carotene of several apocarotenoids, such as 8'-, 10'- and 12'-apo-beta-carotenal and methyl 8'-apo-beta-carotenoate, were investigated in rats, on a molar basis, by both curative-growth assay and liver-storage tests. 2. In the curative-growth assays, on a molar basis the biopotencies of 8'-, 10'- and 12'-apo-beta-carotenal and methyl 8'-apo-beta-carotenoate were 72, 78, 72 and 53% respectively, whereas on a weight basis the corresponding values were 93, 111, 111 and 63%, with respect to beta-carotene taken as 100%. In terms of yield of vitamin A, these values were much lower in the liver-storage tests. 3. When 8'-apo-beta-carotenal was fed, the unchanged aldehyde together with small amounts of the corresponding alcohol and larger proportions of the acid rapidly appeared in the tissues of both rats and chickens. The 8'-apocarotenol, 8'-apocarotenoic acid and its methyl ester were absorbed unchanged. The free acid disappeared most rapidly from the tissues, but its methyl ester persisted in the tissues longest. 4. On the basis of these observations it is suggested that most of an apocarotenal is oxidized to the corresponding acid, which, in turn, is mostly degraded to retinoic acid, with small proportions of it being attacked by the dioxygenase system giving retinal.

Relative ranking: A biased rating

Reviewers' ratings have become one of the most influential parameters when making a decision to purchase or rent the products or services from the online vendors. Star Rating system is the de-facto standard for rating a product. It is regarded as one of the most visually appealing rating systems that directly interact with the consumers; helping them find products they will like to purchase as well as register their views on the product. It offers visual advantage to pick the popular or most rated product. Any system that is not as appealing as star system will have a chance of rejection by online business community. This paper argues that, the visual advantage is not enough to declare star rating system as a triumphant, the success of a ranking system should be measured by how effectively the system helps customers make decisions that they, retrospectively, consider correct. This paper argues and suggests a novel approach of Relative Ranking within the boundaries of star rating system to overcome a few inherent disadvantages the former system comes with. © Springer Science+Business Media B.V. 2010.

Relative stability of DNA as a generic criterion for promoter prediction: whole genome annotation of microbial genomes with varying nucleotide base composition

The rapid increase in genome sequence information has necessitated the annotation of their functional elements, particularly those occurring in the non-coding regions, in the genomic context. Promoter region is the key regulatory region, which enables the gene to be transcribed or repressed, but it is difficult to determine experimentally. Hence an in silico identification of promoters is crucial in order to guide experimental work and to pin point the key region that controls the transcription initiation of a gene. In this analysis, we demonstrate that while the promoter regions are in general less stable than the flanking regions, their average free energy varies depending on the GC composition of the flanking genomic sequence. We have therefore obtained a set of free energy threshold values, for genomic DNA with varying GC content and used them as generic criteria for predicting promoter regions in several microbial genomes, using an in-house developed tool `PromPredict'. On applying it to predict promoter regions corresponding to the 1144 and 612 experimentally validated TSSs in E. coli (50.8% GC) and B. subtilis (43.5% GC) sensitivity of 99% and 95% and precision values of 58% and 60%, respectively, were achieved. For the limited data set of 81 TSSs available for M. tuberculosis (65.6% GC) a sensitivity of 100% and precision of 49% was obtained.

Relative electrical distance concept for evaluation of network reactive power and loss contributions in a deregulated system

With the liberalisation of electricity market it has become very important to determine the participants making use of the transmission network.Transmission line usage computation requires information of generator to load contributions and the path used by various generators to meet loads and losses. In this study relative electrical distance (RED) concept is used to compute reactive power contributions from various sources like generators, switchable volt-amperes reactive(VAR) sources and line charging susceptances that are scattered throughout the network, to meet the system demands. The transmission line charge susceptances contribution to the system reactive flows and its aid extended in reducing the reactive generation at the generator buses are discussed in this paper. Reactive power transmission cost evaluation is carried out in this study. The proposed approach is also compared with other approaches viz.,proportional sharing and modified Y-bus.Detailed case studies with base case and optimised results are carried out on a sample 8-bus system. IEEE 39-bus system and a practical 72-bus system, an equivalent of Indian Southern grid are also considered for illustration and results are discussed.

Thermoelectric power in ultrathin films, quantum wires and carbon nanotubes under classically large magnetic field: Simplified theory and relative comparison

We study the thermoelectric power under classically large magnetic field (TPM) in ultrathin films (UFs), quantum wires (QWs) of non-linear optical materials on the basis of a newly formulated electron dispersion law considering the anisotropies of the effective electron masses, the spin-orbit splitting constants and the presence of the crystal field splitting within the framework of k.p formalism. The results of quantum confined III-V compounds form the special cases of our generalized analysis. The TPM has also been studied for quantum confined II-VI, stressed materials, bismuth and carbon nanotubes (CNs) on the basis of respective dispersion relations. It is found taking quantum confined CdGeAs2, InAs, InSb, CdS, stressed n-InSb and Bi that the TPM increases with increasing film thickness and decreasing electron statistics exhibiting quantized nature for all types of quantum confinement. The TPM in CNs exhibits oscillatory dependence with increasing carrier concentration and the signature of the entirely different types of quantum systems are evident from the plots. Besides, under certain special conditions, all the results for all the materials gets simplified to the well-known expression of the TPM for non-degenerate materials having parabolic energy bands, leading to the compatibility test. (C) 2009 Elsevier B.V. All rights reserved.

Human alveolar T lymphocyte responses to Mycobacterium tuberculosis antigens: role for CD4+ and CD8+ cytotoxic T cells and relative resistance of alveolar macrophages to lysis.

T cell-mediated cytotoxicity against Mycobacterium tuberculosis (MTB)-infected macrophages may be a major mechanism of specific host defense, but little is known about such activities in the lung. Thus, the capacity of alveolar lymphocyte MTB-specific cell lines (AL) and alveolar macrophages (AM) from tuberculin skin test-positive healthy subjects to serve as CTL and target cells, respectively, in response to MTB (H37Ra) or purified protein derivative (PPD) was investigated. Mycobacterial Ag-pulsed AM were targets of blood CTL activity at E:T ratios of > or = 30:1 (51Cr release assay), but were significantly more resistant to cytotoxicity than autologous blood monocytes. PPD- plus IL-2-expanded AL and blood lymphocytes were cytotoxic for autologous mycobacterium-stimulated monocytes at E:T ratios of > or = 10:1. The CTL activity of lymphocytes expanded with PPD was predominantly class II MHC restricted, whereas the CTL activity of lymphocytes expanded with PPD plus IL-2 was both class I and class II MHC restricted. Both CD4+ and CD8+ T cells were enriched in BL and AL expanded with PPD and IL-2, and both subsets had mycobacterium-specific CTL activity. Such novel cytotoxic responses by CD4+ and CD8+ T cells may be a major mechanism of defense against MTB at the site of disease activity.

Carbon sequestration versus bioenergy: A case study from South India exploring the relative land-use efficiency of two options for climate change mitigation

This case study has been carried out as a comparison between two different land-use strategies for climate change mitigation, with possible application within the Clean Development Mechanisms. The benefits of afforestation for carbon sequestration versus for bioenergy production are compared in the context of development planning to meet increasing domestic and agricultural demand for electricity in Hosahalli village, Karnataka, India. One option is to increase the local biomass based electricity generation, requiring an increased biomass plantation area. This option is compared with fossil based electricity generation where the area is instead used for producing wood for non-energy purposes while also sequestering carbon in the soil and standing biomass. The different options have been assessed using the PRO-COMAP model. The ranking of the different options varies depending on the system boundaries and time period. Results indicate that, in the short term (30 years) perspective, the mitigation potential of the long rotation plantation is largest, followed by the short rotation plantation delivering wood for energy. The bioenergy option is however preferred if a long-term view is taken. Short rotation forests delivering wood for short-lived non-energy products have the smallest mitigation potential, unless a large share of the wood products are used for energy purposes (replacing fossil fuels) after having served their initial purpose. If managed in a sustainable manner all of these strategies can contribute to the improvement of the social and environmental situation of the local community. (C) 2009 Elsevier Ltd. All rights reserved.

Thermoelectric Power Under Strong Magnetic Field in Quantum Dots and Quantized Superlattices: Simplified Theory and Relative Comparison

In this paper, we study the thermoelectric power under strong magnetic field (TPSM) in quantum dots (QDs) of nonlinear optical, III-V, II-VI, GaP, Ge, Te, Graphite, PtSb2, zerogap, Lead Germanium Telluride, GaSb, stressed materials, Bismuth, IV-VI, II-V, Zinc and Cadmium diphosphides, Bi2Te3 and Antimony respectively. The TPSM in III-V, II-VI, IV-VI, HgTe/CdTe quantum well superlattices with graded interfaces and effective mass superlattices of the same materials together with the quantum dots of aforementioned superlattices have also been investigated in this context on the basis of respective carrier dispersion laws. It has been found that the TPSM for the said quantum dots oscillates with increasing thickness and decreases with increasing electron concentration in various manners and oscillates with film thickness, inverse quantizing magnetic field and impurity concentration for all types of superlattices with two entirely different signatures of quantization as appropriate in respective cases of the aforementioned quantized structures. The well known expression of the TPSM for wide-gap materials has been obtained as special case for our generalized analysis under certain limiting condition, and this compatibility is an indirect test of our generalized formalism. Besides, we have suggested the experimental method of determining the carrier contribution to elastic constants for nanostructured materials having arbitrary dispersion laws.

Capturability analysis of a geometric guidance law in relative velocity space

In this paper, a relative velocity approach is used to analyze the capturability of a geometric guidance law. Point mass models are assumed for both the missile and the target. The speeds of the missile and target are assumed to remain constant throughout the engagement. Lateral acceleration, obtained from the guidance law, is applied to change the path of the missile. The kinematic equations for engagements in the horizontal plane are derived in the relative velocity space. Some analytical results for the capture region are obtained for non-maneuvering and maneuvering targets. For non-maneuvering targets it is enough for the navigation gain to be a constant to intercept the target, while for maneuvering targets a time varying navigation gain is needed for interception. These results are then verified through numerical simulations.

Clinical reasoning: The relative contribution of identification, interpretation and hypothesis errors to misdiagnosis

The aim of this study was to identify and describe the types of errors in clinical reasoning that contribute to poor diagnostic performance at different levels of medical training and experience. Three cohorts of subjects, second- and fourth- (final) year medical students and a group of general practitioners, completed a set of clinical reasoning problems. The responses of those whose scores fell below the 25th centile were analysed to establish the stage of the clinical reasoning process - identification of relevant information, interpretation or hypothesis generation - at which most errors occurred and whether this was dependent on problem difficulty and level of medical experience. Results indicate that hypothesis errors decrease as expertise increases but that identification and interpretation errors increase. This may be due to inappropriate use of pattern recognition or to failure of the knowledge base. Furthermore, although hypothesis errors increased in line with problem difficulty, identification and interpretation errors decreased. A possible explanation is that as problem difficulty increases, subjects at all levels of expertise are less able to differentiate between relevant and irrelevant clinical features and so give equal consideration to all information contained within a case. It is concluded that the development of clinical reasoning in medical students throughout the course of their pre-clinical and clinical education may be enhanced by both an analysis of the clinical reasoning process and a specific focus on each of the stages at which errors commonly occur.

Enhanced Tetrahedral Ordering of Water Molecules in Minor Grooves of DNA: Relative Role of DNA Rigidity, Nanoconfinement, and Surface Specific Interactions

Confinement and Surface specific interactions call induce Structures otherwise unstable at that temperature and pressure. Here we Study the groove specific water dynamics ill the nucleic acid sequences, poly-AT and poly-GC, in long B-DNA duplex chains by large scale atomistic molecular dynamics simulations, accompanied by thermodynamic analysis. While water dynamics in the major groove remains insensitive to the sequence differences, exactly the opposite is true for the minor groove water. Much slower water dynamics observed in the minor grooves (especially in the AT minor) call be attributed to all enhanced tetrahedral ordering (< t(h)>) of water. The largest value of < t(h)> in the AT minor groove is related to the spine of hydration found in X-ray Structure. The calculated configurational entropy (S-C) of the water molecules is found to be correlated with the self-diffusion coefficient of water in different region via Adam-Gibbs relation D = A exp(-B/TSC), and also with < t(h)>.

The Photoemission from Quantum Wells, Wires and Carbon Nanotubes:Simplified Theory and Relative Comparison

We investigate the photoemission from quantum wells (QWs) in ultrathin films (UFs) and quantum well wires (QWWs) of non-linear optical materials on the basis of a newly formulated electron dispersion law considering the anisotropies of the effective electron masses, the spin-orbit splitting constants and the presence of the crystal field splitting within the framework of k.p formalism. The results of quantum confined Ill-V compounds form the special cases of our generalized analysis. The photoemission has also been studied for quantum confined II-VI, n-GaP, n-Ge, PtSb2, stressed materials and Bismuth on the basis of respective dispersion relations. It has been found taking quantum confined CdGeAS(2), InAs, InSb, CdS, GaP, Ge, PtSb2, stressed n-InSb and B1 that the photoemission exhibits quantized variations with the incident photon energy, changing electron concentration and film thickness, respectively, for all types of quantum confinement. The photoemission from CNs exhibits oscillatory dependence with increasing normalized electron degeneracy and the signature of the entirely different types of quantum systems are evident from the plots. Besides, under certain special conditions, all the results for all the materials gets simplified to the well-known expression of photoemission from non-degenerate semiconductors and parabolic energy bands, leading to the compatibility test.