Functional linear regression analysis for longitudinal data

We propose nonparametric methods for functional linear regression which are designed for sparse longitudinal data, where both the predictor and response are functions of a covariate such as time. Predictor and response processes have smooth random trajectories, and the data consist of a small number of noisy repeated measurements made at irregular times for a sample of subjects. In longitudinal studies, the number of repeated measurements per subject is often small and may be modeled as a discrete random number and, accordingly, only a finite and asymptotically nonincreasing number of measurements are available for each subject or experimental unit. We propose a functional regression approach for this situation, using functional principal component analysis, where we estimate the functional principal component scores through conditional expectations. This allows the prediction of an unobserved response trajectory from sparse measurements of a predictor trajectory. The resulting technique is flexible and allows for different patterns regarding the timing of the measurements obtained for predictor and response trajectories. Asymptotic properties for a sample of $n$ subjects are investigated under mild conditions, as $n\to \infty$, and we obtain consistent estimation for the regression function. Besides convergence results for the components of functional linear regression, such as the regression parameter function, we construct asymptotic pointwise confidence bands for the predicted trajectories. A functional coefficient of determination as a measure of the variance explained by the functional regression model is introduced, extending the standard $R^2$ to the functional case. The proposed methods are illustrated with a simulation study, longitudinal primary biliary liver cirrhosis data and an analysis of the longitudinal relationship between blood pressure and body mass index.Comment: Published at http://dx.doi.org/10.1214/009053605000000660 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Properties of principal component methods for functional and longitudinal data analysis

The use of principal component methods to analyze functional data is appropriate in a wide range of different settings. In studies of ``functional data analysis,'' it has often been assumed that a sample of random functions is observed precisely, in the continuum and without noise. While this has been the traditional setting for functional data analysis, in the context of longitudinal data analysis a random function typically represents a patient, or subject, who is observed at only a small number of randomly distributed points, with nonnegligible measurement error. Nevertheless, essentially the same methods can be used in both these cases, as well as in the vast number of settings that lie between them. How is performance affected by the sampling plan? In this paper we answer that question. We show that if there is a sample of $n$ functions, or subjects, then estimation of eigenvalues is a semiparametric problem, with root-$n$ consistent estimators, even if only a few observations are made of each function, and if each observation is encumbered by noise. However, estimation of eigenfunctions becomes a nonparametric problem when observations are sparse. The optimal convergence rates in this case are those which pertain to more familiar function-estimation settings. We also describe the effects of sampling at regularly spaced points, as opposed to random points. In particular, it is shown that there are often advantages in sampling randomly. However, even in the case of noisy data there is a threshold sampling rate (depending on the number of functions treated) above which the rate of sampling (either randomly or regularly) has negligible impact on estimator performance, no matter whether eigenfunctions or eigenvectors are being estimated.Comment: Published at http://dx.doi.org/10.1214/009053606000000272 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Functional linear regression via canonical analysis

We study regression models for the situation where both dependent and independent variables are square-integrable stochastic processes. Questions concerning the definition and existence of the corresponding functional linear regression models and some basic properties are explored for this situation. We derive a representation of the regression parameter function in terms of the canonical components of the processes involved. This representation establishes a connection between functional regression and functional canonical analysis and suggests alternative approaches for the implementation of functional linear regression analysis. A specific procedure for the estimation of the regression parameter function using canonical expansions is proposed and compared with an established functional principal component regression approach. As an example of an application, we present an analysis of mortality data for cohorts of medflies, obtained in experimental studies of aging and longevity.Comment: Published in at http://dx.doi.org/10.3150/09-BEJ228 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Diet Shapes Mortality Response to Trauma in Old Tephritid Fruit Flies.

Despite the importance of trauma in healthspan and lifespan in humans as well as in non-human species, with one important exception the literature in both gerontology and ecology contains virtually no experimental demographic studies concerned with trauma in any species. We used dietary manipulation [full diet (F) versus sugar-only (S)] to produce four levels of frailty in 55-day old tephritid fruit flies (Anastrepha ludens) that were then subject to the trauma of cage transfer stress (n = 900/sex in each of the 4 treatments). The key results included the following: (1) there is a trauma effect caused by the transfer that depends on previous diet before transfer, new diet after transfer and gender of the fly; (2) males are more vulnerable than females; (3) if initial diet was F, flies are relatively immune against the trauma, and the subsequent diet (F or S) does not matter; (4) however if initial diet was S, then the effect of the trauma depends largely on the diet after the transfer; (5) flies transferred from S to F diets do very well in terms of remaining longevity (i.e. greatest remaining longevity), while flies transferred from S to S diet do poorly (i.e. shortest remaining longevity). We discuss both the strengths and weaknesses of this study and implications of the results

Comunicação e educação ambiental ecosófica: as imagens como possibilidade poética para o desenvolvimento comunitário

When a community university enables the creation of environmental education processes through collaborative educommunication activities (with images) that involve several social groups in order to provide them with access to their right to communication, the question that arises is how can the communicational perspective, which values collective knowledge, point towards a poetic possibility for community development? The objective of this study is to reflect upon the contribution of collaborative communication to development processes. Bibliographical research provides support to the reflections upon the research-intervention that generated the co-creation 28 amateur films. The contributions of Cultural Studies, Community Communication, and Educommunication are used as theoretical references. The processes built collaboratively have enabled community development in the field of Communication, exploring the creative possibilities offered by audiovisual media, which led to new perspectives about the participants themselves and the use of media, about being and acting in groups, and about the environment we inhabit.Cuando una universidad comunitaria posibilita la creación de procesos de educación ambiental a través de actividades colaborativas de educomunicación (utilizando imágenes), que involucran a diversos grupos sociales, con el fin de promover el acceso al derecho a la comunicación de los grupos sociales, la pregunta es ¿cómo la perspectiva comunicacional, que valora el conocimiento colectivo, puede apuntar a una posibilidad poética para el desarrollo comunitario? El objetivo del artículo es reflexionar sobre la contribución de la comunicación colaborativa a los procesos de desarrollo. La investigación bibliográfica apoya las reflexiones sobre la investigación-intervención que generó la experiencia de co-creación de 28 películas de aficionados. Las referencias teóricas se toman de los aportes de los Estudios Culturales, la Comunicación Comunitaria y la Educomunicación. Los procesos construidos colaborativamente posibilitaron el desarrollo comunitario desde el campo de la Comunicación, explorando las posibilidades creativas que ofrecen los audiovisuales, que se reflejaron en nuevas miradas sobre sí mismos y los usos de los medios, sobre el ser y el hacer en grupo y sobre el entorno habitado.Quando uma universidade de caráter comunitário possibilita a criação de processos de educação ambiental por meio de atividades colaborativas de educomunicação (com uso de imagens), que envolvem diversos grupos sociais, a fim de promover o acesso ao direito à comunicação a grupos sociais, questiona-se como a perspectiva comunicacional, que valoriza os saberes coletivos, pode apontar para uma possibilidade poética para o desenvolvimento comunitário? O objetivo do artigo é refletir sobre a contribuição da comunicação colaborativa para os processos de desenvolvimento. A pesquisa bibliográfica apoia as reflexões sobre a pesquisa-intervenção que gerou a experiência de co-criação de 28 filmes amadores. Tomam-se como referenciais teóricos as contribuições dos Estudos Culturais, da Comunicação Comunitária e da Educomunicação. Os processos construídos colaborativamente possibilitaram o desenvolvimento comunitário a partir do campo da Comunicação, explorando as possibilidades criativas que os audiovisuais oferecem, os quais refletiram-se em novos olhares sobre si e os usos das mídias, sobre o estar e o fazer em grupo e sobre o ambiente habitado

Fungal cyclooligomer depsipeptides: From classical biochemistry to combinatorial biosynthesis

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.This review surveys the biological activities and the iterative and recursive biosynthetic mechanisms of fungal cyclooligomer depsipeptides, and their structural diversification by various combinatorial biosynthetic methods

DNA-activated protein kinase functions in a newly observed S phase checkpoint that links histone mRNA abundance with DNA replication

DNA and histone synthesis are coupled and ongoing replication is required to maintain histone gene expression. Here, we expose S phase–arrested cells to the kinase inhibitors caffeine and LY294002. This uncouples DNA replication from histone messenger RNA (mRNA) abundance, altering the efficiency of replication stress–induced histone mRNA down-regulation. Interference with caffeine-sensitive checkpoint kinases ataxia telangiectasia and Rad3 related (ATR)/ataxia telangiectasia mutated (ATM) does not affect histone mRNA down- regulation, which indicates that ATR/ATM alone cannot account for such coupling. LY294002 potentiates caffeine's ability to uncouple histone mRNA stabilization from replication only in cells containing functional DNA-activated protein kinase (DNA-PK), which indicates that DNA-PK is the target of LY294002. DNA-PK is activated during replication stress and DNA-PK signaling is enhanced when ATR/ATM signaling is abrogated. Histone mRNA decay does not require Chk1/Chk2. Replication stress induces phosphorylation of UPF1 but not hairpin-binding protein/stem-loop binding protein at S/TQ sites, which are preferred substrate recognition motifs of phosphatidylinositol 3-kinase–like kinases, which indicates that histone mRNA stability may be directly controlled by ATR/ATM- and DNA-PK–mediated phosphorylation of UPF1