Modeling continuous auxiliary covariate data in generalized linear mixed models using the kernel smoother

Auxiliary covariate data are often collected in biomedical studies when the primary exposure variable is only assessed on a subset of the study subjects. In this study, we investigate a semiparametric‐estimated likelihood estimation for the generalized linear mixed models (GLMM) in the presence of a continuous auxiliary variable. We use a kernel smoother to handle continuous auxiliary data. The method can be used to deal with missing or mismeasured covariate data problems in a variety of applications when an auxiliary variable is available and cluster sizes are not too small. Simulation study results show that the proposed method performs better than that which ignores the random effects in GLMM and that which only uses data in the validation data set. We illustrate the proposed method with a real data set from a recent environmental epidemiology study on the maternal serum 1,1‐dichloro‐2,2‐bis(p‐chlorophenyl) ethylene level in relationship to preterm births.     

Continuous infusion of cholecystokinin and meal pattern in the rat

Purified natural cholecystokinin (CCK-33) was infused continuously for two days at a rate of 5.9 μg/hr in two rats trained to bar-press for food (Noyes pellet 45 mg) on a fixed ratio of five bar presses to obtain one pellet. The animals also received control surgery and were tested in the operant chamber for two days, one prior to and the other following the CCK-33 treatment. CCK-33 suppressed the number of meals, the total amount of food eaten, and the total duration of time spent eating. However, the size of each meal and the rate of intake were not affected. The CCK effect did not interact with the light-dark phases of diurnal cycle. It appears that a major effect of continuous systemic elevation of CCK-33 is to reduce food intake by prolonging the satiety period rather than by decreasing the individual meal size.     

Apical membrane localization of the adenomatous polyposis coli tumor suppressor protein and subcellular distribution of the beta-catenin destruction complex in polarized epithelial cells

The adenomatous polyposis coli (APC) protein is implicated in the majority of hereditary and sporadic colon cancers. APC is known to function as a tumor suppressor through downregulation of beta-catenin as part of a high molecular weight complex known as the beta-catenin destruction complex. The molecular composition of the intact complex and its site of action in the cell are still not well understood. Reports on the subcellular localization of APC in various cell systems have differed significantly and have been consistent with an association with a cytosolic complex, with microtubules, with the nucleus, or with the cortical actin cytoskeleton. To better understand the role of APC and the destruction complex in colorectal cancer, we have begun to characterize and isolate these complexes from confluent polarized human colon epithelial cell monolayers and other epithelial cell types. Subcellular fractionation and immunofluorescence microscopy reveal that a predominant fraction of APC associates tightly with the apical plasma membrane in a variety of epithelial cell types. This apical membrane association is not dependent on the mutational status of either APC or beta-catenin. An additional pool of APC is cytosolic and fractionates into two distinct high molecular weight complexes, 20S and 60S in size. Only the 20S fraction contains an appreciable portion of the cellular axin and small but detectable amounts of glycogen synthase kinase 3beta and beta-catenin. Therefore, it is likely to correspond to the previously characterized beta-catenin destruction complex. Dishevelled is almost entirely cytosolic, but does not significantly cofractionate with the 20S complex. The disproportionate amount of APC in the apical membrane and the lack of other destruction complex components in the 60S fraction of APC raise questions about whether these pools of APC take part in the degradation of beta-catenin, or alternatively, whether they could be involved in other functions of the protein that still must be determined.     

Glucose-induced period-doubling cascade in the electrical activity of pancreatic β-cells

 In the presence of stimulatory concentrations of glucose, the membrane potential of pancreatic β-cells may experience a transition from periods of rapid spike-like oscillations alternating with a pseudo-steady state to spike-only oscillations. Insulin secretion from β-cells closely correlates the periods of spike-like oscillations. The purpose of this paper is to study the mathematical structure which underlines this transitional stage in a pancreatic β-cell model. It is demonstrated that the transition can be chaotic but becomes more and more regular with increase in glucose. In particular, the system undergoes a reversed period-doubling cascade leading to the spike-only oscillations as the glucose concentration crosses a threshold. The transition interval in glucose concentration is estimated to be extremely small in terms of the rate of change for the calcium dynamics in the β-cells. The methods are based on the theory of unimodal maps and the geometric and asymptotic theories of singular perturbations. Received: 25 October 1996/Revised version: 18 August 1997     

Thermal and chemical resistance of Lactobacillus casei and Lactobacillus paracasei bacteriophages

AIMS: The survival of two collection Lactobacillus casei and L. paracasei bacteriophages when subjected to thermal and chemical treatments was investigated. METHODS AND RESULTS: Thermal resistance was evaluated by heating phage suspensions at 63, 72 and 90 degrees C in three different media [Tris-magnesium gelatin (TMG) buffer: 10 mmol l(-1) Tris-Cl, 10 mmol l(-1) MgSO(4) and 0.1% w/v gelatin; Man Rogosa Sharpe (MRS) broth and reconstituted nonfat dry skim milk (RSM)]. A marked heat sensitivity was evident in both phages, as 15 min at 72 degrees C was enough to completely inactivate (6 log(10) reduction) them. No clear influence was demonstrated by the suspension media. The phages also showed similar resistance to biocides. Peracetic acid and sodium hypochlorite (800 ppm) were the most effective ones, destroying the phages within 5 min. Concentrations of 75 and 100% ethanol were not suitable to inactivate phage particles even after 45 min. Isopropanol did not show an effect on phage viability. CONCLUSIONS: The data obtained in this work are important to design more effective control procedures in order to inactivate phages in dairy plants and laboratories. SIGNIFICANCE AND IMPACT OF THE STUDY: This work will contribute to enhance the background knowledge about phages of probiotic bacteria.     

Ty1 insertions in intergenic regions of the genome of Saccharomyces cerevisiae transcribed by RNA polymerase III have no detectable selective effect

The retrotransposon Ty1 of Saccharomyces cerevisiae inserts preferentially into intergenic regions in the vicinity of RNA polymerase III-transcribed genes. It has been suggested that this preference has evolved to minimize the deleterious effects of element transposition on the host genome, and thus to favor their evolutionary survival. This presupposes that such insertions have no selective effect. However, there has been no direct test of this hypothesis. Here we construct a series of strains containing single Ty1 insertions in the vicinity of tRNA genes, or in the rDNA cluster on chromosome XII, which are otherwise isogenic to strain 337, containing zero Ty1 elements. Competition experiments between 337 and the strains containing single Ty1 insertions revealed that in all cases, the Ty1 insertions have no selective effect in rich medium. These results are thus consistent with the hypothesis that the insertion site preference of Ty1 elements has evolved to minimize the deleterious effects of transposition on the host genome.     

Entrainment of circadian programs

Of the three defining properties of circadian rhythmicity--persisting free-running rhythm, temperature compensation, and entrainment--the last is often poorly understood by many chronobiologists. This paper gives an overview of entrainment. Where have we been? Where are we now? Whence should we be going? Particular emphasis is given to a discussion of the Discrete vs. Continuous models for entrainment. We provide an integrated mechanism for entrainment from a limit-cycle perspective.     

Analysis of the behaviour of<Emphasis Type="Italic"> Dictyostelium discoideum</Emphasis> in immobilised state by means of continuous cultivation

The social amoeba Dictyostelium discoideum is amenable to cultivation in the immobilised state most simply by colonisation of porous supports. An analysis of the growth behaviour of D. discoideum in the immobilised state is reported. For this purpose, D. discoideum was cultivated in continuously operated reactors in a suspension culture (homogeneous system) and immobilised on a porous support (heterogeneous system). Thus, it is possible to compare homogeneous and heterogeneous systems under steady-state conditions. Immobilisation was achieved by the colonisation of porous glass beads (SIRAN). Simple models are applied in order to describe the growth behaviour of fractions of both the cells in free suspension and the cells inside the porous carrier. This analysis shows that D. discoideum inside the pores grows at a rate of only about 10% compared with that in free solution. The consequence of this behaviour is discussed in terms of reactor performance.