Active Set methods for solving large sample average approximations of chance constrained optimisation problems

This article describes a novel approach to chance-constrained programming based on the sample average approximation (SAA) method. Recent work focuses on heuristic approximations to the SAA problem and we introduce a novel approach which improves on some existing methods. Our Active Set method allows one to solve SAAs of chance-constrained programs with very large numbers of scenarios quickly. We demonstrate that increasing the number of scenarios is more important than improving accuracy with small numbers of scenarios. We use an example of the portfolio selection problem to demonstrate the relative performance of previous and new methods. Extending the Active Set method to an integer-programming model further highlights its applicability and further improves over previous approaches.Comment: 26 pages, 7 figures, This paper sets forth the material presented at the Decision Making Under Uncertainty workshop held at the University of Queensland, 11 July 202

Interactive Coupling of TELEMAC with the Open Source Water Quality Model 143 DELWAQ

Water Qualit

The Accuracy of Survival Time Prediction for Patients with Glioma Is Improved by Measuring Mitotic Spindle Checkpoint Gene Expression

Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC) genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK) significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001), and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67) labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time

Membrane mixing and dynamics in hybrid POPC/PBd-PEO lipid/block co-polymer giant vesicles

Lipids and block copolymers can individually self-assemble into vesicles, each with their own particular benefits and limitations. Combining polymers with lipids allows for further optimisation of the vesicle membranes for bionanotechnology applications. Here, POPC lipid is mixed with poly(1,2-butadiene-block-ethylene oxide) of two different molecular weights (PBd22-PEO14, Mr = 1800 g.mol-1 and PBd12-PEO11, Mr = 1150 g.mol-1) in order to investigate, how increasing the polymer fraction affects membrane mixing, hydration and fluidity. Intensity contributions of fluorescently labelled lipid and polymer within mixed GUV membranes confirm membrane homogeneity within the hybrids. General polarisation measurements of Laurdan in GUVs showed little change in membrane hydration as polymer fraction is increased, which suggests good structurally compatibility between lipids and polymers that gives rise to well-mixed vesicles. Membrane fluidity in hybrid GUVs was found to decrease non-linearly with increasing polymer fraction. However, the diffusion coefficients for the fluorescent polymer in hybrid membranes did not change significantly with increasing polymer content. While increasing the polymer fraction does reduce the movement of lipids through a polymer-rich matrix, insignificant difference in diffusion coefficients of the polymer suggests that its diffusion is minimally affected by increasing lipid composition in the range studied. These results lay further foundations for the wider development of hybrid vesicles with controlled properties for advanced biotechnologies

Detergent-free functionalisation of hybrid vesicles with membrane proteins using SMALPs

Hybrid vesicles (HVs) that consist of mixtures of block copolymers and lipids are robust biomimetics of liposomes, providing a valuable building block in bionanotechnology, catalysis and synthetic biology. However, functionalisation of HVs remains laborious and expensive, creating a significant current challenge in the field. Here, using a new approach of extraction with styrene-maleic acid lipid particles (SMALPs), we show that a membrane protein (cytochrome bo3) directly transfers into HVs with an efficiency of 73.9 ± 13.5% and without the requirement of any detergent, long incubation times or mechanical disruption. Interestingly, direct transfer of membrane proteins using this approach was not possible into liposomes. This suggests that the HVs are more amenable than liposomes to membrane protein incorporation from a SMALP system. Finally, we show that this transfer method is not limited to cytochrome bo3 and can also be performed with complex membrane protein mixtures

High resolution membrane structures within hybrid lipid-polymer vesicles revealed by combining x-ray scattering and electron microscopy

Hybrid vesicles consisting of phospholipids and block-copolymers are increasingly finding applications in science and technology. Herein, small angle X-ray scattering (SAXS) and cryo-electron tomography (cryo-ET) were used to obtain detailed structural information about hybrid vesicles with different ratios of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and poly(1,2-butadiene-block-ethylene oxide) (PBd22-PEO14, Ms = 1800 gmol-1) . Using single particle analysis (SPA) we were able to further interpret the information gained from SAXS and cryo-ET experiments, showing that increasing PBd22-PEO14 mole fraction increases the membrane thickness from 52 Å for a pure lipid system to 97 Å for pure PBd22-PEO14 vesicles. We find two vesicle populations with different membrane thicknesses in hybrid vesicle samples. As these lipids and polymers are known to homogeneously mix, bistability is inferred between weak and strong interdigitation regimes of PBd22-PEO14 within the hybrid membranes. It is hypothesized that membranes of intermediate structure are not energetically favourable. Therefore, upon formation, each vesicle selects one of these two membrane structures, which are assumed to have comparable free energies. We conclude that, by combining biophysical methods, an accurate determination of the influence of composition on the structural properties of hybrid membranes is achieved, revealing that two distinct membranes structures can coexist in homogeneously mixed lipid-polymer hybrid vesicles

Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas

Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations