Parameter estimation of kinetic models from metabolic profiles: two-phase dynamic decoupling method

Motivation: Time-series measurements of metabolite concentration have become increasingly more common, providing data for building kinetic models of metabolic networks using ordinary differential equations (ODEs). In practice, however, such time-course data are usually incomplete and noisy, and the estimation of kinetic parameters from these data is challenging. Practical limitations due to data and computational aspects, such as solving stiff ODEs and finding global optimal solution to the estimation problem, give motivations to develop a new estimation procedure that can circumvent some of these constraints. Results: In this work, an incremental and iterative parameter estimation method is proposed that combines and iterates between two estimation phases. One phase involves a decoupling method, in which a subset of model parameters that are associated with measured metabolites, are estimated using the minimization of slope errors. Another phase follows, in which the ODE model is solved one equation at a time and the remaining model parameters are obtained by minimizing concentration errors. The performance of this two-phase method was tested on a generic branched metabolic pathway and the glycolytic pathway of Lactococcus lactis. The results showed that the method is efficient in getting accurate parameter estimates, even when some information is missing. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Hierarchical Assembly of Nucleic Acid/Coiled-Coil Peptide Nanostructures

DNA and peptides are two of the most commonly used biomolecules for building self-assembling materials, but few examples exist of hybrid nanostructures that contain both components. Here we report the modification of two peptides that comprise a coiled-coil heterodimer pair with unique DNA handles in order to link DNA origami nanostructures bearing complementary strands into micrometer-long one-dimensional arrays. We probed the effect of number of coils on self-assembly and demonstrated the formation of structures through multiple routes: one-pot assembly, formation of dimers and trimers and an alternating copolymer of two different origami structures, and stepwise assembly of purified structures with coiled-coil conjugates. Our results demonstrate the successful merging of two distinct self-assembly modes to create hybrid bionanomaterials expected to have a range of potential applications in the future

VITALAS at TRECVID-2009

This paper describes the participation of VITALAS in the TRECVID-2009 evaluation where we submitted runs for the High-Level Feature Extraction (HLFE) and Interactive Search tasks. For the HLFE task, we focus on the evaluation of low-level feature sets and fusion methods. The runs employ multiple low-level features based on all available modalities (visual, audio and text) and the results show that use of such features improves the retrieval eectiveness signicantly. We also use a concept score fusion approach that achieves good results with reduced low-level feature vector dimensionality. Furthermore, a weighting scheme is introduced for cluster assignment in the \bag-of-words" approach. Our runs achieved good performance compared to a baseline run and the submissions of other TRECVID-2009 participants. For the Interactive Search task, we focus on the evaluation of the integrated VITALAS system in order to gain insights into the use and eectiveness of the system's search functionalities on (the combination of) multiple modalities and study the behavior of two user groups: professional archivists and non-professional users. Our analysis indicates that both user groups submit about the same total number of queries and use the search functionalities in a similar way, but professional users save twice as many shots and examine shots deeper in the ranked retrieved list.The agreement between the TRECVID assessors and our users was quite low. In terms of the eectiveness of the dierent search modalities, similarity searches retrieve on average twice as many relevant shots as keyword searches, fused searches three times as many, while concept searches retrieve even up to ve times as many relevant shots, indicating the benets of the use of robust concept detectors in multimodal video retrieval. High-Level Feature Extraction Runs 1. A VITALAS.CERTH-ITI 1: Early fusion of all available low-level features. 2. A VITALAS.CERTH-ITI 2: Concept score fusion for ve low-level features and 100 concepts, text features and bag-of-words with color SIFT descriptor based on dense sampling. 3. A VITALAS.CERTH-ITI 3: Concept score fusion for ve low-level features and 100 concepts combined with text features. 4. A VITALAS.CERTH-ITI 4: Weighting scheme for bag-of-words based on dense sampling of the color SIFT descriptor. 5. A VITALAS.CERTH-ITI 5: Baseline run, bag-of-words based on dense sampling of the color SIFT descriptor. Interactive Search Runs 1. vitalas 1: Interactive run by professional archivists 2. vitalas 2: Interactive run by professional archivists 3. vitalas 3: Interactive run by non-professional users 4. vitalas 4: Interactive run by non-professional user

Carbon sequestration via wood burial

To mitigate global climate change, a portfolio of strategies will be needed to keep the atmospheric CO2 concentration below a dangerous level. Here a carbon sequestration strategy is proposed in which certain dead or live trees are harvested via collection or selective cutting, then buried in trenches or stowed away in above-ground shelters. The largely anaerobic condition under a sufficiently thick layer of soil will prevent the decomposition of the buried wood. Because a large flux of CO2 is constantly being assimilated into the world's forests via photosynthesis, cutting off its return pathway to the atmosphere forms an effective carbon sink

Phase Separation of Crystal Surfaces: A Lattice Gas Approach

We consider both equilibrium and kinetic aspects of the phase separation (``thermal faceting") of thermodynamically unstable crystal surfaces into a hill--valley structure. The model we study is an Ising lattice gas for a simple cubic crystal with nearest--neighbor attractive interactions and weak next--nearest--neighbor repulsive interactions. It is likely applicable to alkali halides with the sodium chloride structure. Emphasis is placed on the fact that the equilibrium crystal shape can be interpreted as a phase diagram and that the details of its structure tell us into which surface orientations an unstable surface will decompose. We find that, depending on the temperature and growth conditions, a number of interesting behaviors are expected. For a crystal in equilibrium with its vapor, these include a low temperature regime with logarithmically--slow separation into three symmetrically--equivalent facets, and a higher temperature regime where separation proceeds as a power law in time into an entire one--parameter family of surface orientations. For a crystal slightly out of equilibrium with its vapor (slow crystal growth or etching), power--law growth should be the rule at late enough times. However, in the low temperature regime, the rate of separation rapidly decreases as the chemical potential difference between crystal and vapor phases goes to zero.Comment: 16 pages (RevTex 3.0); 12 postscript figures available on request ([email protected]). Submitted to Physical Review E. SFU-JDSDJB-94-0

Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism

Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.)Glenn Foundation for Medical ResearchNational Institutes of Health (U.S.) (Grant 5-P50-090381-09)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Burroughs Wellcome FundSmith Family FoundationDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.) (Grant 1R01DK075850-01)National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Reversible self-assembly of superstructured networks

Soft structures in nature, such as protein assemblies, can organize reversibly into functional and often hierarchical architectures through noncovalent interactions. Molecularly encoding this dynamic capability in synthetic materials has remained an elusive goal. We report on hydrogels of peptide-DNA conjugates and peptides that organize into superstructures of intertwined filaments that disassemble upon the addition of molecules or changes in charge density. Experiments and simulations demonstrate that this response requires large-scale spatial redistribution of molecules directed by strong noncovalent interactions among them. Simulations also suggest that the chemically reversible structures can only occur within a limited range of supramolecular cohesive energies. Storage moduli of the hydrogels change reversibly as superstructures form and disappear, as does the phenotype of neural cells in contact with these materials

Thermally stable single atom Pt/m-Al2O3 for selective hydrogenation and CO oxidation

Single-atom metal catalysts offer a promising way to utilize precious noble metal elements more effectively, provided that they are catalytically active and sufficiently stable. Herein, we report a synthetic strategy for Pt single-atom catalysts with outstanding stability in several reactions under demanding conditions. The Pt atoms are firmly anchored in the internal surface of mesoporous Al2O3, likely stabilized by coordinatively unsaturated pentahedral Al3+ centres. The catalyst keeps its structural integrity and excellent performance for the selective hydrogenation of 1,3-butadiene after exposure to a reductive atmosphere at 200 °C for 24 h. Compared to commercial Pt nanoparticle catalyst on Al2O3 and control samples, this system exhibits significantly enhanced stability and performance for n-hexane hydro-reforming at 550 °C for 48 h, although agglomeration of Pt single-atoms into clusters is observed after reaction. In CO oxidation, the Pt single-atom identity was fully maintained after 60 cycles between 100 and 400 °C over a one-month period