Streamlined mean field variational Bayes for longitudinal and multilevel data analysis

Streamlined mean field variational Bayes algorithms for efficient fitting and inference in large models for longitudinal and multilevel data analysis are obtained. The number of operations is linear in the number of groups at each level, which represents a two orders of magnitude improvement over the naïve approach. Storage requirements are also lessened considerably. We treat models for the Gaussian and binary response situations. Our algorithms allow the fastest ever approximate Bayesian analyses of arbitrarily large longitudinal and multilevel datasets, with little degradation in accuracy compared with Markov chain Monte Carlo. The modularity of mean field variational Bayes allows relatively simple extension to more complicated scenarios.     

Comparison of various procedures for estimation of the classification error in discriminance analysis

The practical use of classification methods depends, for the majority of cases, on whether it is possible to obtain evidence how newly appearing objects of unknown classes-membership can be allocated on the basis of a classifier established by a training sample. In the present paper several error estimation methods are presented and compared with each other. It is shown by means of a practical example in which way the number of characteristics used in the discrimination affects the classification error. Discriminance functions calculated from many characteristics yield a higher error rate than those from fewer characteristics. From the comparison of the error rates and computing times involved in the individual methods recommendations for the selection of practicable estimation methods are given.     

Absolute configuration of cis-5,6-dihydrodiol enantiomers derived from helical conformers of 1,12-dimethylbenz[a]anthracene

1,12-Dimethylbenz[a]anthracene (1,12-DMBA) cis-5,6-dihydrodiol was synthesized by oxidation of 1,12-DMBA with osmium tetroxide in pyridine in low yield (less than or equal to 3%) and was purified by sequential use of reversed-phase and normal-phase HPLC. Two pairs of 1,12-DMBA cis-5,6-dihydrodiol enantiomers, derived from P (right-handed helix) and M (left-handed helix) conformers, were eluted as a single chromatographic peak on both reversed-phase and normal-phase HPLC. However, these four enantiomers were resolved by sequential use of two chiral stationary phase (CSP) HPLC columns. CSP (Pirkle type I) columns were packed with either (R)-N-(3,5-dinitrobenzoyl)phenylglycine or (S)-N-(3,5-dinitrobenzoyl)leucine, which is ionically bonded to gamma-aminopropylsilanized silica. Absolute configurations of enantiomers were determined by comparing their circular dichroism spectra with those of conformationally similar cis-5,6-dihydrodiol enantiomers of 4-methylbenz[a]anthracene and 7,12-dimethylbenz[a]anthracene with known absolute stereochemistry.     

Responses to UV-B radiation in Trifolium repens L. – physiological links to plant productivity and water availability

This study used comparisons across nine populations of Trifolium repens (white clover) in conjunction with drought to examine physiological responses to ultraviolet‐B radiation (UV‐B). Plants were exposed for 12 weeks to supplementation with 13.3 kJ m^?2 d^?1 UV‐B, accompanied by 4 weeks of drought under controlled environmental conditions. UV‐B increased the levels of UV‐B‐absorbing compounds and of flavonol glycosides and this effect was synergistically enhanced by water stress. These changes were more pronounced for the ortho‐dihydroxylated quercetin, rather than the monohydroxylated kaempferol glycosides. UV‐B increased leaf water potential (ψ_L) by 16% under drought and proline levels by 23% under well‐watered conditions. The intraspecific comparisons showed that higher UV‐B‐induced levels of UV‐B‐absorbing compounds, of quercetin glycosides and of ψ_L were linked to lower plant productivity and to higher UV‐B tolerance under well‐watered conditions. These findings suggest that: (1) slow‐growing T. repens ecotypes adapted to other stresses have higher capacity for physiological acclimation to UV‐B; and (2) that these attributes also contribute to decreased UV‐B sensitivity under drought.     

Living in a World of Smart Everyday Objects—Social,Economic, and Ethical Implications

Visions of Pervasive Computing and ambient intelligence involve integrating tiny microelectronic processors and sensors into everyday objects in order to make them “smart.” Smart things can explore their environment, communicate with other smart things, and interact with humans, therefore helping users to cope with their tasks in new, intuitive ways. Although many concepts have already been tested out as prototypes in field trials, the repercussions of such extensive integration of computer technology into our everyday lives are difficult to predict. This article is a first attempt to classify the social, economic, and ethical implications of this development.     

The involvement of mnn4 and mnn6 mutations in mannosylphosphorylation of O-linked oligosaccharide in yeast Saccharomyces cerevisiae

The structure of O-linked acidic oligosaccharide from Saccharomyces cerevisiae was analyzed. The chitinase, exclusively O-glycosylated extracelluar protein, was purified from strains mnn1, mnn1 mnn4, mnn1 mnn6 and Δkre2 and the oligosaccharides were hydrolyzed by O-linked sugar chain specific hydrazinolysis. The mannosylphosphorylated mannotriose (M3-P-M) was detected in strain mnn1, but not in the other three strains (mnn1 mnn4, mnn1 mnn6 and Δkre2). α-Mannosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry of mannosylphosphorylated mannotriose revealed that mannosylphosphate was attached to a middle mannose of α-1,2-linked mannotriose. This result indicates that the mnn4 and mnn6 mutations affect the mannosylphosphorylation of O-linked oligosaccharide, together with that of N-linked oligosaccharide. The amount of mannosylphosphorylated mannotriose was 7% of total O-linked oligosaccharides (20% of neutral mannotriose) of chitinase in strain mnn1.     

High titer methyl ketone production with tailored Pseudomonas taiwanensis VLB120

Methyl ketones present a group of highly reduced platform chemicals industrially produced from petroleum-derived hydrocarbons. They find applications in the fragrance, flavor, pharmacological, and agrochemical industries, and are further discussed as biodiesel blends. In recent years, intense research has been carried out to achieve sustainable production of these molecules by re-arranging the fatty acid metabolism of various microbes. One challenge in the development of a highly productive microbe is the high demand for reducing power. Here, we engineered Pseudomonas taiwanensis VLB120 for methyl ketone production as this microbe has been shown to sustain exceptionally high NAD(P)H regeneration rates. The implementation of published strategies resulted in 2.1 g L_aq⁻¹ methyl ketones in fed-batch fermentation. We further increased the production by eliminating competing reactions suggested by metabolic analyses. These efforts resulted in the production of 9.8 g L_aq⁻¹ methyl ketones (corresponding to 69.3 g L_org⁻¹ in the in situ extraction phase) at 53% of the maximum theoretical yield. This represents a 4-fold improvement in product titer compared to the initial production strain and the highest titer of recombinantly produced methyl ketones reported to date. Accordingly, this study underlines the high potential of P. taiwanensis VLB120 to produce methyl ketones and emphasizes model-driven metabolic engineering to rationalize and accelerate strain optimization efforts.     

High-performance liquid chromatography (HPLC) determination of inosine, a potential biomarker for initial cardiac ischaemia, using isolated mouse hearts

Each year in the USA approximately 7-8 million patients with non-traumatic chest pain come to hospital emergency rooms. It is estimated that approximately 2-5% of these patients are experiencing cardiac ischaemia, but due to the shortcomings of the available testing methods they are incorrectly diagnosed and discharged without appropriate therapy having been provided. Preliminary data with a globally ischaemic mouse heart model has demonstrated that endogenous inosine might be a potential biomarker of initial cardiac ischaemia before cardiac tissue necrosis. A high-performance liquid chromatographic diode array detection (HPLC-DAD) method was utilized for the detection and quantification of inosine in Krebs-Henseleit (Krebs) buffer solution perfusing from surgically removed and isolated mouse hearts undergoing global cardiac ischaemia. A C₁₈ column at a flow rate of 0.6 ml min^-1 with an aqueous mobile phase of trifluoroacetic acid (0.05% trifluoroacetic acid in deionized water, pH 2.2, v/v) and methanol gradient was used for component separation. The assay detection limit for inosine in Krebs buffer solution was 500 ng ml^-1 using a 100-µl neat injection. The HPLC results were used to determine total cardiac effluxed inosine into the Krebs effluent for each mouse during oxidative stress and compared with the per cent cardiac ventricular functional recovery rate to determine if a relationship exists amongst this cardiovascular parameter during periods of cardiac oxidative stress.     

Dual-beam difference spectroelectrochemistry

An optically transparent thin-layer electrode with carbon fibers as the working electrode is described for use in dual-beam difference spectroscopy. This cell simplifies obtaining the spectrum of a species of interest in the presence of mediators, cofactors, etc. The spectroelectrochemistry of cytochrome c with a large excess of spectrally interfering mediator present is shown.