Reservoir Flooding Optimization by Control Polynomial Approximations

In this dissertation, we provide novel parametrization procedures for water-flooding production optimization problems, using polynomial approximation techniques. The methods project the original infinite dimensional controls space into a polynomial subspace. Our contribution includes new parameterization formulations using natural polynomials, orthogonal Chebyshev polynomials and Cubic spline interpolation. We show that the proposed methods are well suited for black-box approach with stochastic global-search method as they tend to produce smooth control trajectories, while reducing the solution space size. We demonstrate their efficiency on synthetic two-dimensional problems and on a realistic 3-dimensional problem. By contributing with a new adjoint method formulation for polynomial approximation, we implemented the methods also with gradient-based algorithms. In addition to fine-scale simulation, we also performed reduced order modeling, where we demonstrated a synergistic effect when combining polynomial approximation with model order reduction, that leads to faster optimization with higher gains in terms of Net Present Value. Finally, we performed gradient-based optimization under uncertainty. We proposed a new multi-objective function with three components, one that maximizes the expected value of all realizations, and two that maximize the averages of distribution tails from both sides. The new objective provides decision makers with the flexibility to choose the amount of risk they are willing to take, while deciding on production strategy or performing reserves estimation (P10;P50;P90)

Neisseria meningitidis and cytomegalovirus simultaneous detection in the filmarray meningitis/encephalitis panel and its clinical relevance

A BioFire FilmArray Meningitis/Encephalitis test was performed on a 7-month old child suspected for bacterial meningitis. Two pathogens were detected, Neisseria meningitidis and cytomegalovirus (CMV). We verified the filmarray meningitis/encephalitis test by pan-bacterial assay to test for Neisseria meningitidis and CMV viral load test for the CMV detection. Pan-bacterial confirmed presence of N. meningitidis, but CMV was not detected by the CMV viral load test. Together with the manifestations of high fever, vomiting, diffuse petechial rash, bulging fontanel, and leukocytosis, it is a clear case of meningococcal meningitis, while CMV detection had no clinical relevance

Dual Fatty Acyl Modification Determines the Localization and Plasma Membrane Targeting of CBL/CIPK Ca2+ Signaling Complexes in Arabidopsis[W]

Arabidopsis thaliana calcineurin B–like proteins (CBLs) interact specifically with a group of CBL-interacting protein kinases (CIPKs). CBL/CIPK complexes phosphorylate target proteins at the plasma membrane. Here, we report that dual lipid modification is required for CBL1 function and for localization of this calcium sensor at the plasma membrane. First, myristoylation targets CBL1 to the endoplasmic reticulum. Second, S-acylation is crucial for endoplasmic reticulum-to-plasma membrane trafficking via a novel cellular targeting pathway that is insensitive to brefeldin A. We found that a 12–amino acid peptide of CBL1 is sufficient to mediate dual lipid modification and to confer plasma membrane targeting. Moreover, the lipid modification status of the calcium sensor moiety determines the cellular localization of preassembled CBL/CIPK complexes. Our findings demonstrate the importance of S-acylation for regulating the spatial accuracy of Ca2+-decoding proteins and suggest a novel mechanism that enables the functional specificity of calcium sensor/kinase complexes

How prenylation and S-acylation regulate subcellular targeting and function of ROP GTPases

Rho of Plants (ROP) small G proteins function at discrete domains of the plasma and possibly endo membranes. ROPs are synthesized as soluble proteins and their attachment to membranes and partitioning in membrane microdomains are facilitated by the posttranslational lipid modifications prenylation and/or S-acylation. Based on their amino acid sequences, ROPs can be classified into two major subgroups: type-I ROPs terminate with a canonical CaaX box motif and are prenylated primarily by geranyl-geranyltransferase-I (GGT-I) and to a lesser extent by farnesyltransferase (FT). Type-II ROPs terminate with a plant specific GC-CG box domain and are attached to the plasma membrane by stable S-acylation. In addition, type-I and possibly also type-II ROPs undergo activation dependent transient S-acylation in the G-domain and consequent partitioning into lipid rafts. Surprisingly, although geranylgeranylation is required for the membrane attachment of type-I ROPs and the γ subunits of heterotrimeric G proteins, Arabidopsis mutants lacking GGT-I function have a mild phenotype compared to wild type plants. The mild phenotype of the ggt-I mutants suggested that farnesylation by FT may compensate for the loss of GGT-I function and that possibly the prenylated type-I and S-acylated type-II ROPS have some overlapping functions. In a paper recently published in Plant Physiology1 we examined the role of the prenyl group type in type-I ROP function and membrane interaction dynamics and the functional redundancy between type-I and type-II ROPs. This study complements a second paper in which we examined the role of G-domain transient S-acylation in the membrane interaction dynamics and signaling by type-I ROPs.2 Together these two studies provide a framework for realizing the role of prenylation and S-acylation in subcellular targeting, membrane interaction dynamics and signaling by ROP GTPases

Identification of MEDIATOR16 as the Arabidopsis COBRA suppressor MONGOOSE1.

We performed a screen for genetic suppressors of cobra, an Arabidopsis mutant with defects in cellulose formation and an increased ratio of unesterified/esterified pectin. We identified a suppressor named mongoose1 (mon1) that suppressed the growth defects of cobra, partially restored cellulose levels, and restored the esterification ratio of pectin to wild-type levels. mon1 was mapped to the MEDIATOR16 (MED16) locus, a tail mediator subunit, also known as SENSITIVE TO FREEZING6 (SFR6). When separated from the cobra mutation, mutations in MED16 caused resistance to cellulose biosynthesis inhibitors, consistent with their ability to suppress the cobra cellulose deficiency. Transcriptome analysis revealed that a number of cell wall genes are misregulated in med16 mutants. Two of these genes encode pectin methylesterase inhibitors, which, when ectopically expressed, partially suppressed the cobra phenotype. This suggests that cellulose biosynthesis can be affected by the esterification levels of pectin, possibly through modifying cell wall integrity or the interaction of pectin and cellulose

Activation Status-Coupled Transient S Acylation Determines Membrane Partitioning of a Plant Rho-Related GTPase

ROPs or RACs are plant Rho-related GTPases implicated in the regulation of a multitude of signaling pathways that function at the plasma membrane by virtue of posttranslational lipid modifications. The relationship between ROP activation status and membrane localization has not been established. Here we demonstrate that endogenous ROPs, as well as a transgenic His(6)-green fluorescent protein (GFP)-AtROP6 fusion protein, were partitioned between Triton X-100-soluble and -insoluble membranes. In contrast, an activated His(6)-GFP-Atrop6(CA) mutant protein accumulated exclusively in detergent-resistant membranes. GDP induced accumulation of ROPs in Triton-soluble membranes, whereas GTPγS induced accumulation of ROPs in detergent-resistant membranes. Recombinant wild-type and constitutively active AtROP6 isoforms were purified from Arabidopsis plants, and their lipids were cleaved and analyzed by gas chromatography-coupled mass spectrometry. In Triton-soluble membranes, wild-type AtROP6 was only prenylated, primarily by geranylgeranyl. The activated AtROP6 that accumulated in detergent-resistant membranes was modified by prenyl and acyl lipids. The acyl lipids were identified as palmitic and stearic acids. In agreement, activated His(6)-GFP-Atrop6(CA)mS(156) in which cysteine(156) was mutated into serine accumulated in Triton-soluble membranes. These findings show that upon GTP binding and activation, AtROP6 and possibly other ROPs are transiently S acylated, which induces their partitioning into detergent-resistant membranes