The study of mammalian metabolism through NMR-based metabolomics

High-resolution NMR spectroscopy has been widely used to monitor metabolism almost since the technique's development. It is now one of the principle technologies used in metabolomics, to profile the metabolite compliment of a cell, tissue, organism, or biofluid. This chapter describes how tissue extracts are prepared for NMR spectroscopy and, in particular, focuses on two approaches based on perchloric acid and methanol/chloroform extractions. This is followed by a description of key NMR experiments that can be used to profile tissue extracts, biofluids, or intact tissues. While these NMR techniques should be optimized for a particular sample set, we provide some tried and tested starting parameters for these experiments which should allow the user to acquire good quality spectra

Gaussian Process Planning with Lipschitz Continuous Reward Functions: Towards Unifying Bayesian Optimization, Active Learning, and Beyond

This paper presents a novel nonmyopic adaptive Gaussian process planning (GPP) framework endowed with a general class of Lipschitz continuous reward functions that can unify some active learning/sensing and Bayesian optimization criteria and offer practitioners some flexibility to specify their desired choices for defining new tasks/problems. In particular, it utilizes a principled Bayesian sequential decision problem framework for jointly and naturally optimizing the exploration-exploitation trade-off. In general, the resulting induced GPP policy cannot be derived exactly due to an uncountable set of candidate observations. A key contribution of our work here thus lies in exploiting the Lipschitz continuity of the reward functions to solve for a nonmyopic adaptive epsilon-optimal GPP (epsilon-GPP) policy. To plan in real time, we further propose an asymptotically optimal, branch-and-bound anytime variant of epsilon-GPP with performance guarantee. We empirically demonstrate the effectiveness of our epsilon-GPP policy and its anytime variant in Bayesian optimization and an energy harvesting task.Comment: 30th AAAI Conference on Artificial Intelligence (AAAI 2016), Extended version with proofs, 17 page

Reformulation of fine translucent porcelain

A low-clay version of fine translucent china was designed to have desired properties and acceptable behaviour during manufacture. Low-clay contents of 10 to ISw/o were employed to reduce the deterious effects of preferential clay particle alignment and its adverse effect on colour. For example, alignment of clay particles in cast wares causes anisotropic drying and firing shrinkages and these cause distortion. Replacing clay with a pre fired body with low Fe and Ti contents, as in the present case, allowed a very white material to be produced. The prefired body was made with calcium carbonate, aluminium trihydroxide, quartz and a small fluxing addition of an hydrated magnesIUm carbonate. Desification of a whiteware is enhanced by increasing volume fraction of the viscous liquid and reducing by its viscosity. Both of these also enhance sagging. Consequently, compositional change cannot on its own lead to the favourable combination of high density, required to give translucency, with little sagging, that will allow wares to be fired without significant distortion. It was found by trail and error that use of finer particles reduced the sagging occurring in the densification heat treatment and enhanced densification. This finding allowed the body to be designed so that it densified without sagging excessively. After establishing this important result, an iterative approach was employed to produce a ware that was very white, translucent, had the required thermal expansion coefficient for glaze fitting, shrank acceptably during the first firing and did not sag during the second firing that stimulated glost firing. The finding on sagging was applied to an anorthite/mullite porcelain body that was under development. This body was also made with a low-clay content and the same prefired body. This whitware has potential to replace bone china and hard porcelain for use in the servere service conditions of hotels and restaurants. It has a higher fracture toughness than hard porcelain but has the same scratch resistant glaze and is more resistant to thermal shock. The sagging of the anorthite/mullite porcelain was substantially reduced while the body was densified. This was achieved by using a combination of finer particles and a reduction in the liquid-phase content that developed during firing

Gaussian Process Planning with Lipschitz Continuous Reward Functions

This paper presents a novel nonmyopic adaptive Gaussian process planning (GPP) framework endowed with a general class of Lipschitz continuous reward functions that can unify some active learning/sensing and Bayesian optimization criteria and offer practitioners some flexibility to specify their desired choices for defining new tasks/problems. In particular, it utilizes a principled Bayesian sequential decision problem framework for jointly and naturally optimizing the exploration-exploitation trade-off. In general, the resulting induced GPP policy cannot be derived exactly due to an uncountable set of candidate observations. A key contribution of our work here thus lies in exploiting the Lipschitz continuity of the reward functions to solve for a nonmyopic adaptive ε-optimal GPP (ε-GPP) policy. To plan in real time, we further propose an asymptotically optimal, branch-and-bound anytime variant of ε-GPP with performance guarantee. We empirically demonstrate the effectiveness of our ε-GPP policy and its anytime variant in Bayesian optimization and an energy harvesting task.Singapore-MIT Alliance for Research and Technology (SMART) (52 R-252-000-550-592

Metabolomic study of the LDL receptor null mouse fed a high-fat diet reveals profound perturbations in choline metabolism that are shared with ApoE null mice

Failure to express or expression of dysfunctional low-density lipoprotein receptors (LDLR) causes familial hypercholesterolemia in humans, a disease characterized by elevated blood cholesterol concentrations, xanthomas, and coronary heart disease, providing compelling evidence that high blood cholesterol concentrations cause atherosclerosis. In this study, we used 1H nuclear magnetic resonance spectroscopy to examine the metabolic profiles of plasma and urine from the LDLR knockout mice. Consistent with previous studies, these mice developed hypercholesterolemia and atherosclerosis when fed a high-fat/cholesterol/cholate-containing diet. In addition, multivariate statistical analysis of the metabolomic data highlighted significant differences in tricarboxylic acid cycle and fatty acid metabolism, as a result of high-fat/cholesterol diet feeding. Our metabolomic study also demonstrates that the effect of high-fat/cholesterol/cholate diet, LDLR gene deficiency, and the diet-genotype interaction caused a significant perturbation in choline metabolism, notably the choline oxidation pathway. Specifically, the loss in the LDLR caused a marked reduction in the urinary excretion of betaine and dimethylglycine, especially when the mice are fed a high-fat/cholesterol/cholate diet. Furthermore, as we demonstrate that these metabolic changes are comparable with those detected in ApoE knockout mice fed the same high-fat/cholesterol/cholate diet they may be useful for monitoring the onset of atherosclerosis across animal models

Kinetic and reactor modelling of lipases catalyzed (R,S)-1-phenylethanol resolution

This study was focused on the development of a kinetic model and a reactor model for the enzymatic resolution of (R,S)-1-phenylethanol. The reaction progress curves catalyzed by immobilized lipases, ChiroCLEC-PC in batch stirred tank reactor were used to develop the kinetic model. The resolution followed Ping-Pong Bi-Bi mechanism with the inhibition of lauric acid, (R,S)-1-phenylethanol and water. The validity of the model was verified by fitting it to another experimental data catalyzed by immobilized lipases, Chirazyme L2, c.-f., C3, lyo at the same reaction conditions. The rate equation was then applied for the development of reactor model in a recirculated packed bed reactor system. The overall effectiveness factor and Peclet number were used to determine the mass transfer and axial dispersion limitation in the reactor performance. The reactor model was verified by fitting it to the larger scale reactor data with the correlation coefficient value more than 0.99