Mixed Model Discrete Regression

Models and estimention procedures are given for linear regression models in discrete distributions when the regression contains both fixed and random effects. The methods are developed for discrete variables with typically a small number of possible outcomes such as occurs in ordinal regression. The method is applied to a problem arising in the comparison of microbiological test methods.     

Dechlorination and spectral changes associated with bacterial degradation of 2-(2-methyl-4-chlorophenoxy)propionic acid

Summary The bacterial degradation of mecoprop (2-(2-methyl-4-chlorophenoxy)propionic acid) was studied using a mixed culture under aerobic conditions. The release of chlorine from mecoprop indicated incomplete degradation (75%), which did not proceed to completion upon extended incubation. The UV absorbance initially increased and this was associated with spectral distortion of the shoulder and trough regions and a slight shift in the maximum wavelength of absorption. GC-MS analysis indicated that 4-chloro-2-methylphenol was an intermediate in the degradative pathway of mecoprop. The GC-MS data also suggested the formation of other phenolic compounds with repositioned chloro-and methylgroups.     

Preparation and in vitro and in vivo evaluation of quercetin-loaded mixed micelles for oral delivery

Quercetin (QT) is a plant polyphenol with various pharmacological properties. However, the low water solubility limits its therapeutic efficacy. In the present study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed micelles were developed and characterized, and the effect of the formulation on improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed micelles were prepared by thin film hydration-direct dissolution and optimized by uniform design. The optimal formulation possessed high drug loading (12.6%) and entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A low critical micelle concentration indicated that the micelles were stable, and they showed a sustained release pattern, as determined in vitro in simulated gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed the C_max and AUC_0–24 were 1.8-fold and 1.6-fold higher than the QT suspension. The present results indicate that QT-loaded ST/P123 micelles are potential candidates to improve the solubility and oral bioavailability of QT.     

A stage‐wise approach for the analysis of multi‐environment trials

Plant breeders and variety testing agencies routinely test candidate genotypes (crop varieties, lines, test hybrids) in multiple environments. Such multi‐environment trials can be efficiently analysed by mixed models. A single‐stage analysis models the entire observed data at the level of individual plots. This kind of analysis is usually considered as the gold standard. In practice, however, it is more convenient to use a two‐stage approach, in which experiments are first analysed per environment, yielding adjusted means per genotype, which are then summarised across environments in the second stage. Stage‐wise approaches suggested so far are approximate in that they cannot fully reproduce a single‐stage analysis, except in very simple cases, because the variance–covariance matrix of adjusted means from individual environments needs to be approximated by a diagonal matrix. This paper proposes a fully efficient stage‐wise method, which carries forward the full variance–covariance matrix of adjusted means from the individual environments to the analysis across the series of trials. Provided the variance components are known, this method can fully reproduce the results of a single‐stage analysis. Computations are made efficient by a diagonalisation of the residual variance–covariance matrix, which necessitates a corresponding linear transformation of both the first‐stage estimates (e.g. adjusted means and regression slopes for plot covariates) and the corresponding design matrices for fixed and random effects. We also exemplify the extension of the general approach to a three‐stage analysis. The method is illustrated using two datasets, one real and the other simulated. The proposed approach has close connections with meta‐analysis, where environments correspond to centres and genotypes to medical treatments. We therefore compare our theoretical results with recently published results from a meta‐analysis.     

Spatiotemporal heterogeneity and clinical challenge of pancreatic neuroendocrine tumors

During the course of pancreatic neuroendocrine tumors (NETs), they generally become more heterogeneous with individual cells exhibiting distinct molecular fingerprints. This heterogeneity manifests itself through an unequal distribution of genetically-variant, tumor cell subpopulations within disease locations (i.e., spatial heterogeneity) or changes in the genomic landscape over time (i.e., temporal heterogeneity); these characteristics complicate clinical diagnosis and treatment. Effective, feasible tumor heterogeneity detection and eradication methods are essential to overcome the clinical challenges of pancreatic NETs. This review explores the molecular fingerprints of pancreatic NETs and the spectrum of tumoral heterogeneity. We then describe the challenges of assessing heterogeneity by liquid biopsies and imaging modalities and the therapeutic challenges for pancreatic NETs. In general, navigating these challenges, refining approaches for translational research, and ultimately improving patient care are available once we have a better understanding of intratumoral spatiotemporal heterogeneity.     

Mixed function oxidases and herbivore polyphagy: the devil's advocate position

Abstract. 1. Evidence used to support the theory that mixed function oxidases (MFOs) are important in the survival of polyphagous herbivores is briefly reviewed. This evidence includes data on patterns of variation in MFO activity among species and among developmental stages within species. It also includes data on induction of MFO activity by plant compounds and metabolism of plant cornpounds by MFOs.
2. It is argued that the evidence presently available does not offer strong support of the theory because key pieces of information are lacking. Evidence which tends to refute the theory is reviewed and discussed.
3. Experiments are proposed which could more rigorously test the theory.     

The importance of bees as pollinators in the short corolla bromeliad Aechmea caudata in southern Brazil

The majority of bromeliad species are pollinated by vertebrates, mainly hummingbirds and bats. However, bees are among the most frequent visitors in some short-corolla species with ornithophilous features, but only few studies identified insects as pollinators of these bromeliads. The importance of visitors for pollination success in Aechmea caudata (Bromeliaceae) was determined through the frequency and pollination effectiveness (measured as seed set/single visit) of its visitors in a secondary Atlantic forest area in southern Brazil. Aechmea caudata is self-incompatible and therefore pollinator-dependent. A total of 16 species were recorded visiting their flowers. Bees were the most rich and frequent taxon (91% of 647 visits). Bombus morio was the most frequent species (41%). Although the floral features of A. caudata, such as scentless, tubular corollas, yellow and red flowers, and nectar secretion during the whole diurnal anthesis, are related to ornithophily, the single hummingbird species Thalurania glaucopis failed to pollinate the flowers. Its low frequency (2.5%) apparently did not promote the pollen flux between conspecific bromeliads. Pollination tests showed that no seeds developed after hummingbird visits. Seeds were formed only at flowers visited by B. morio. We discuss our findings by contrasting them with the results on the similar and sympatric A. lindenii and by emphasizing the importance of bees for pollination of bromeliads with short corolla. Our results show that pollination effectiveness together with frequency data are necessary to analyze the complex interactions between plants and their flower visitors.     

Energy dependence on discharge mode of Izhikevich neuron driven by external stimulus under electromagnetic induction

Energy supply plays a key role in metabolism and signal transmission of biological individuals, neurons in a complex electromagnetic environment must be accompanied by the absorption and release of energy. In this paper, the discharge mode and the Hamiltonian energy are investigated within the Izhikevich neuronal model driven by external signals in the presence of electromagnetic induction. It is found that multiple electrical activity modes can be observed by changing external stimulus, and the Hamiltonian energy is more dependent on the discharge mode. In particular, there is a distinct shift and transition in the Hamiltonian energy when the discharge mode is switched quickly. Furthermore, the amplitude of periodic stimulus signal has a greater effect on the neuronal energy compared to the angular frequency, and the average Hamiltonian energy decreases when the discharge rhythm becomes higher. Based on the principle of energy minimization, the system should choose the minimum Hamiltonian energy when maintaining various trigger states to reduce the metabolic energy of signal processing in biological systems. Therefore, our results give the possible clues for predicting and selecting appropriate parameters, and help to understand the sudden and paroxysmal mechanisms of epilepsy symptoms.     

Using biological traits to assess how urbanization filters plant species of small woodlands

Question: Which biological traits (persistence, regeneration, dispersion traits and resource requirements) may explain the distribution of woodland flora along an urban–rural gradient? Location: The study was carried out in three medium‐sized conurbations of north‐western France: Angers, Nantes and Rennes. Methods: We sampled the vegetation of 36 small woodlands of about 1.5 ha composed of non‐planted vegetation along an urban–rural gradient. We characterized the position of woodlands along the urban–rural gradient by examining adjacent land cover. By using an ordination analysis (RLQ), we analysed which traits out of –23 tested were related to the contrasted distribution of species along the urban–rural gradient. Results: Species that are more likely to be found in urban woodlands than rural woodlands have different persistence traits (higher specific leaf area, more often rosette or semi‐rosette form, less underground vegetative multiplication), resource requirements (affinity for base‐rich and fertile soils) and regeneration traits (short life‐span). Dispersion traits were not related to the distribution of species along the urban–rural gradient. Conclusions: Our approach identifies traits that can help to determine the vulnerability of forest species as a result of the environmental changes that follow urbanization. Limiting the influence of the urban environment on habitat quality (particularly disturbance and soil enrichment) is likely to be of major importance in maintaining the plant biodiversity in woodlands.