Conditional Maximum Likelihood Estimation Following a Group Sequential Test

We consider estimation after a group sequential test. An estimator that is unbiased or has small bias may have substantial conditional bias (Troendle and Yu, 1999, Coburger and Wassmer, 2001). In this paper we derive the conditional maximum likelihood estimators of both the primary parameter and a secondary parameter, and investigate their properties within a conditional inference framework. The method applies to both the usual and adaptive group sequential test designs. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

POPULATION STRUCTURE IN ZAMIA DEBILIS (ZAMIACEAE) I. SIZE CLASSES,LEAF PHENOLOGY,AND LEAF TURNOVER

Population structure, leaf phenology and leaf turnover were followed over a 29-month period in Zamia debilis L.f. ex Aiton (Zamiaceae), an understory species in the Cambalache Forest in northern Puerto Rico. It was not possible to determine plant age or to measure the subterranean stems; size classes based on leaf number and leaf × leaflet number indices were used to determine population structure. Despite seasonal and year to year fluctuations in leaf number at the individual and population level, population profiles remained relatively constant. At any one time, over 50% of the population was composed of unbranched individuals with one or two leaves. Only 7% of the plants were branched. Plants with seven or more leaves comprised at a maximum 8% of the population, but accounted for 28% of the total foliage. Size classes based on leaf number and on a leaf × leaflet index gave approximately reverse J-shaped curves typical of trees with shade tolerant seedlings and saplings. New leaves emerged throughout the year, with a peak at the beginning of the rainy season in May or June and lowest production during the dry months of February through April. Average leaf life expectancy was approximately 2.3 years. Leaf death occurred over an extended period of time by the loss of individual leaflets. Patterns in leaf production and loss differed between few- and many-leaved plants. On the average, as the number of mature leaves on a plant increased, time between emergence of new leaves decreased. In many-leaved plants more than one event of new leaf emergence per year was common. Individuals with one to three mature leaves and individuals with four or more mature leaves differed in their response to water stress: few-leaved plants generally reduced the rate of new leaf production and retained old leaves longer. Plants with more than three leaves continued to produce new leaves, but the rate of leaf mortality increased so that most had a net leaf loss. There was no evidence that leaf emergence or retention were affected by cone production or seed maturation.     

A line-balancing strategy for designing flexible assembly systems

We present a rough-cut analysis tool that quickly determines a few potential cost-effective designs at the initial design stage of flexible assembly systems (FASs) prior to a detailed analysis such as simulation. It uses quantitative methods for selecting and configuring the components of an FAS suitable for medium to high volumes of several similar products. The system is organized as a series of assembly stations linked with an automated material-handling system moving parts in a unidirectional flow. Each station consists of a single machine or of identical parallel machines. The methods exploit the ability of flexible hardware to switch almost instantaneously from product to product. Our approach is particularly suitable where the product mix is expected to be stable, since we combine the hardware-configuration phase with the task-allocation phase. For the required volume of products, we use integer programming to select the number of stations and the number of machines at each station and to allocate tasks to stations. We use queueing network analysis, which takes into account the mean and variance of processing times among different products to determine the necessary capacity of the material-handling system. We iterate between the two analyses to find the combined solution with the lowest costs. Work-in-process costs are also included in the analysis. Computational results are presented.     

Monolayer cultures of dispersed cells from bovine anterior pituitary: responses to synthetic hypophysiotropic peptides.

Cells were dispersed from bovine anterior pituitary glands, by digestion with collagenase, and cultured. After 4 days the cell monolayers were incubated with fresh medium containing synthetic hypophysiotropic peptides for 2, 6, or 20 h, and hormone released into the medium was estimated by radioimmunoassay. After 2 h, thyroid releasing hormone (TRH) stimulated the release of thyroid-stimulating hormone (TSH) up to eightfold, and of prolactin (PRL) and follicle-stimulating hormone (FSH) about twofold at a minimal effective concentration of 1 ng/ml; enhanced growth hormone (GH) release was not apparent until 20 h, and release of luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) was unaffected. Luteinizing hormone releasing hormone (LH-RH) enhanced release of LH maximally (three- to fourfold) during a 2 h incubation and was effective at 0.1 ng/ml; FSH release was significantly enhanced by about 50% above control level. Growth hormone release inhibiting hormone (GH-RIH)(somatostatin) showed significant effects only in the 20 h incubation; GH release was inhibited by 50% and release of PRL was slightly, but significantly, enhanced. Pituitary cell monolayers apparently permit maximal expression of releasing activities inherent in the hypothalamic hormones.     

Synapse maturation and structural plasticity at Drosophila neuromuscular junctions

The Drosophila larval neuromuscular junction has recently emerged as a powerful model system to characterize the cellular and molecular events involved in the formation and flexibility of synapses. The combination of molecular, genetic, electrophysiological and anatomical approaches has revealed, for example, the functional significance of the discs-large gene product (a novel synapse-organizing protein) in the nervous system. This protein is involved in the clustering of at least one ion channel and in the structural modification of glutamatergic synapses during target muscle growth. The manipulation of the genes encoding ion channels, components of second-messenger cascades, and cell adhesion molecules is beginning to tease apart the mechanisms underlying structural synaptic plasticity.     

Distribution dynamics of South American savanna birds in response to Quaternary climate change

Several lines of evidence suggest that savannas currently distributed disjointedly in the southern and northern portions of South America might have been connected and disconnected many times during the Quaternary climatic fluctuations. Here, we investigated how climate change since the Last Interglacial may have modified the distribution of bird species associated with South American savannas. We evaluated the connections between South America's savannas using 10 broadly distributed species and the impact of climate changes in community composition using 18 species endemic to Cerrado. We fit ecological niche models to each of the 28 bird species to compare the potential distribution patterns for the Last Interglacial (120 kyr BP), the Last Glacial Maximum (21 kyr BP) and the present. Our results corroborated hypotheses of past connections between northern and southern blocks of savannas through three hypothetical corridors that existed along the Andes, Atlantic Coast and through central Amazonia. In addition, our results also suggested the existence of a fourth plausible corridor located along the Madeira River, crossing Amazonia from the southwest to the northeast. Finally, our analysis showed significant changes in the community composition dynamics of endemic Cerrado species. Our results further reinforce the notion that climate change has major impacts on the distribution of savanna species.     

A loss of insulin-like growth factor-2 imprinting is modulated by CCCTC-binding factor down-regulation at senescence in human epithelial cells

The imprinted insulin-like growth factor-2 (IGF2) gene is an auto/paracrine growth factor expressed only from the paternal allele in adult tissues. In tissues susceptible to aging-related cancers, including the prostate, a relaxation of IGF2 imprinting is found, suggesting a permissive role for epigenetic alterations in cancer development. To determine whether IGF2 imprinting is altered in cellular aging and senescence, human prostate epithelial and urothelial cells were passaged serially in culture to senescence. Allelic analyses using an IGF2 polymorphism demonstrated a complete conversion of the IGF2 imprint status from monoallelic to biallelic, in which the development of senescence was associated with a 10-fold increase in IGF2 expression. As a mechanism, a 2-fold decrease in the binding of the enhancer-blocking element CCCTC-binding factor (CTCF) within the intergenic IGF2-H19 region was found to underlie this switch to biallelic IGF2 expression in senescent cells. This decrease in CTCF binding was associated with reduced CTCF expression in senescent cells. No de novo increases in methylation at the IGF2 CTCF binding site were seen. The forced down-regulation of CTCF expression using small interfering RNA in imprinted prostate cell lines resulted in an increase in IGF2 expression and a relaxation of imprinting. Our data suggest a novel mechanism for IGF2 imprinting regulation, that is, the reduction of CTCF expression in the control of IGF2 imprinting. We also demonstrate that altered imprinting patterns contribute to changes in gene expression in aging cells.