Reconciliation of metabolites and biochemical reactions for metabolic networks.

Genome-scale metabolic network reconstructions are now routinely used in the study of metabolic pathways, their evolution and design. The development of such reconstructions involves the integration of information on reactions and metabolites from the scientific literature as well as public databases and existing genome-scale metabolic models. The reconciliation of discrepancies between data from these sources generally requires significant manual curation, which constitutes a major obstacle in efforts to develop and apply genome-scale metabolic network reconstructions. In this work, we discuss some of the major difficulties encountered in the mapping and reconciliation of metabolic resources and review three recent initiatives that aim to accelerate this process, namely BKM-react, MetRxn and MNXref (presented in this article). Each of these resources provides a pre-compiled reconciliation of many of the most commonly used metabolic resources. By reducing the time required for manual curation of metabolite and reaction discrepancies, these resources aim to accelerate the development and application of high-quality genome-scale metabolic network reconstructions and models.

Iowa Communications Network Performance Report, FY 2007

Agency Performance Report

Heterogeneous 40Ar* distributions in naturally deformed muscovite: in situ UV-laser ablation evidence for micro structurally controlled intragrain diffusion

Micas are commonly used in Ar-40/Ar-39 thermochronological studies of variably deformed rocks yet the physical basis by which deformation may affect radiogenic argon retention in mica is poorly constrained. This study examines the relationship between deformation and deformation-induced microstructures on radiogenic argon retention in muscovite, A combination of furnace step-heating and high-spatial resolution in situ UV-laser ablation Ar-40/Ar-39 analyses are reported for deformed muscovites sampled from a granitic pegmatite vein within the Siviez-Mischabel Nappe, western Swiss Alps (Penninic domain, Brianconnais unit). The pegmatite forms part of the Variscan (similar to 350 Ma) Alpine basement and exhibits a prominent Alpine S-C fabric including numerous mica `fish' that developed under greenschist facies metamorphic conditions, during the dominant Tertiary Alpine tectonic phase of nappe emplacement. Furnace step-heating of milligram quantities of separated muscovite grains yields an Ar-40/Ar-39 age spectrum with two distinct staircase segments but without any statistical plateau, consistent with a previous study from the same area. A single (3 X 5 mm) muscovite porphyroclast (fish) was investigated by in situ UV-laser ablation. A histogram plot of 170 individual Ar-40/Ar-39 UV-laser ablation ages exhibit a range from 115 to 387 Ma with modes at approximately 340 and 260 Ma. A variogram statistical treatment of the (40)Ad/Ar-39 results reveals ages correlated with two directions; a highly correlated direction at 310 degrees and a lesser correlation at 0 degrees relative to the sense of shearing. Using the highly correlated direction a statistically generated (Kriging method) age contour map of the Ar-40/Ar-39 data reveals a series of elongated contours subparallel to the C-surfaces which where formed during Tertiary nappe emplacement. Similar data distributions and slightly younger apparent ages are recognized in a smaller mica fish. The observed intragrain age variations are interpreted to reflect the partial loss of radiogenic argon during Alpine (similar to 35 Ma) greenschist facies metamorphism. One-dirnensional diffusion modelling results are consistent with the idea that the zones of youngest apparent age represent incipient shear band development within the mica porphyroclasts, thus providing a network of fast diffusion pathways. During Alpine greenschist facies metamorphism the incipient shear bands enhanced the intragrain loss of radiogenic argon. The structurally controlled intragrain age variations observed in this investigation imply that deformation has a direct control on the effective length scale for argon diffusion, which is consistent with the heterogeneous nature of deformation. (C) 2001 Elsevier Science B.V. All rights reserved.

PhD Students’ Research Group Social Capital in Two Countries: A Clustering Approach with Duocentred Network Measures

The article examines the structure of the collaboration networks of research groups where Slovenian and Spanish PhD students are pursuing their doctorate. The units of analysis are student-supervisor dyads. We use duocentred networks, a novel network structure appropriate for networks which are centred around a dyad. A cluster analysis reveals three typical clusters of research groups. Those which are large and belong to several institutions are labelled under a bridging social capital label. Those which are small, centred in a single institution but have high cohesion are labelled as bonding social capital. Those which are small and with low cohesion are called weak social capital groups. Academic performance of both PhD students and supervisors are highest in bridging groups and lowest in weak groups. Other variables are also found to differ according to the type of research group. At the end, some recommendations regarding academic and research policy are drawn

Network revenue management with product-specific no-shows

Revenue management practices often include overbooking capacity to account for customerswho make reservations but do not show up. In this paper, we consider the network revenuemanagement problem with no-shows and overbooking, where the show-up probabilities are specificto each product. No-show rates differ significantly by product (for instance, each itinerary andfare combination for an airline) as sale restrictions and the demand characteristics vary byproduct. However, models that consider no-show rates by each individual product are difficultto handle as the state-space in dynamic programming formulations (or the variable space inapproximations) increases significantly. In this paper, we propose a randomized linear program tojointly make the capacity control and overbooking decisions with product-specific no-shows. Weestablish that our formulation gives an upper bound on the optimal expected total profit andour upper bound is tighter than a deterministic linear programming upper bound that appearsin the existing literature. Furthermore, we show that our upper bound is asymptotically tightin a regime where the leg capacities and the expected demand is scaled linearly with the samerate. We also describe how the randomized linear program can be used to obtain a bid price controlpolicy. Computational experiments indicate that our approach is quite fast, able to scale to industrialproblems and can provide significant improvements over standard benchmarks.

Mapping of the genes coding for the two major vaccinia virus core polypeptides.

We have mapped the genes coding for two major structural polypeptides of the vaccinia virus core by hybrid selection and transcriptional mapping. First, RNA was selected by hybridization to restriction fragments of the vaccinia virus genome, translated in vitro and the products were immunoprecipitated with antibodies against the two polypeptides. This approach allowed us to map the genes to the left hand end of the largest Hind III restriction fragment of 50 kilobase pairs. Second, transcriptional mapping of this region of the genome revealed the presence of the two expected RNAs. Both RNAs are transcribed from the leftward reading strand and the 5'-ends of the genes are separated by about 7.5 kilobase pairs of DNA. Thus, two genes encoding structural polypeptides with a similar location in the vaccinia virus particle are clustered at approximately 105 kilobase pairs from the left hand end of the 180 kilobase pair vaccinia virus genome.

A randomized concave programming method for choice network revenue management

Models incorporating more realistic models of customer behavior, as customers choosing froman offer set, have recently become popular in assortment optimization and revenue management.The dynamic program for these models is intractable and approximated by a deterministiclinear program called the CDLP which has an exponential number of columns. However, whenthe segment consideration sets overlap, the CDLP is difficult to solve. Column generationhas been proposed but finding an entering column has been shown to be NP-hard. In thispaper we propose a new approach called SDCP to solving CDLP based on segments and theirconsideration sets. SDCP is a relaxation of CDLP and hence forms a looser upper bound onthe dynamic program but coincides with CDLP for the case of non-overlapping segments. Ifthe number of elements in a consideration set for a segment is not very large (SDCP) can beapplied to any discrete-choice model of consumer behavior. We tighten the SDCP bound by(i) simulations, called the randomized concave programming (RCP) method, and (ii) by addingcuts to a recent compact formulation of the problem for a latent multinomial-choice model ofdemand (SBLP+). This latter approach turns out to be very effective, essentially obtainingCDLP value, and excellent revenue performance in simulations, even for overlapping segments.By formulating the problem as a separation problem, we give insight into why CDLP is easyfor the MNL with non-overlapping considerations sets and why generalizations of MNL posedifficulties. We perform numerical simulations to determine the revenue performance of all themethods on reference data sets in the literature.

Dietary folates and cancer risk in a network of case-control studies.

Background Folate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers. Patients and methods The study is based on a network of case-control studies conducted in Italy and Switzerland in 1991-2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors. Results For a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 μg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking. Conclusions Our data support a real inverse association of dietary folate intake with the risk of several common cancers.

A tractable consideration set structure for network revenue management

Models incorporating more realistic models of customer behavior, as customers choosing from an offerset, have recently become popular in assortment optimization and revenue management. The dynamicprogram for these models is intractable and approximated by a deterministic linear program called theCDLP which has an exponential number of columns. When there are products that are being consideredfor purchase by more than one customer segment, CDLP is difficult to solve since column generationis known to be NP-hard. However, recent research indicates that a formulation based on segments withcuts imposing consistency (SDCP+) is tractable and approximates the CDLP value very closely. In thispaper we investigate the structure of the consideration sets that make the two formulations exactly equal.We show that if the segment consideration sets follow a tree structure, CDLP = SDCP+. We give acounterexample to show that cycles can induce a gap between the CDLP and the SDCP+ relaxation.We derive two classes of valid inequalities called flow and synchronization inequalities to further improve(SDCP+), based on cycles in the consideration set structure. We give a numeric study showing theperformance of these cycle-based cuts.

Fuzzy coding in constrained ordinations

Canonical correspondence analysis and redundancy analysis are two methods of constrained ordination regularly used in the analysis of ecological data when several response variables (for example, species abundances) are related linearly to several explanatory variables (for example, environmental variables, spatial positions of samples). In this report I demonstrate the advantages of the fuzzy coding of explanatory variables: first, nonlinear relationships can be diagnosed; second, more variance in the responses can be explained; and third, in the presence of categorical explanatory variables (for example, years, regions) the interpretation of the resulting triplot ordination is unified because all explanatory variables are measured at a categorical level.

Diabetes mellitus and cancer risk in a network of case-control studies.

Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without-adjusted for major identified confounding factors for the cancers considered through logistic regression models-were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer. [Table: see text] [Table: see text].

Equivalence of piecewise-linear approximation and Lagrangian relaxation for network revenue management

The network revenue management (RM) problem arises in airline, hotel, media,and other industries where the sale products use multiple resources. It can be formulatedas a stochastic dynamic program but the dynamic program is computationallyintractable because of an exponentially large state space, and a number of heuristicshave been proposed to approximate it. Notable amongst these -both for their revenueperformance, as well as their theoretically sound basis- are approximate dynamic programmingmethods that approximate the value function by basis functions (both affinefunctions as well as piecewise-linear functions have been proposed for network RM)and decomposition methods that relax the constraints of the dynamic program to solvesimpler dynamic programs (such as the Lagrangian relaxation methods). In this paperwe show that these two seemingly distinct approaches coincide for the network RMdynamic program, i.e., the piecewise-linear approximation method and the Lagrangianrelaxation method are one and the same.