Nonparametric regression penalizing deviations from additivity

Due to the curse of dimensionality, estimation in a multidimensional nonparametric regression model is in general not feasible. Hence, additional restrictions are introduced, and the additive model takes a prominent place. The restrictions imposed can lead to serious bias. Here, a new estimator is proposed which allows penalizing the nonadditive part of a regression function. This offers a smooth choice between the full and the additive model. As a byproduct, this penalty leads to a regularization in sparse regions. If the additive model does not hold, a small penalty introduces an additional bias compared to the full model which is compensated by the reduced bias due to using smaller bandwidths. For increasing penalties, this estimator converges to the additive smooth backfitting estimator of Mammen, Linton and Nielsen [Ann. Statist. 27 (1999) 1443-1490]. The structure of the estimator is investigated and two algorithms are provided. A proposal for selection of tuning parameters is made and the respective properties are studied. Finally, a finite sample evaluation is performed for simulated and ozone data.Comment: Published at http://dx.doi.org/10.1214/009053604000001246 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Inner ear tissue preservation by rapid freezing: improving fixation by high-pressure freezing and hybrid methods

In the preservation of tissues in as ‘close to life’ state as possible, rapid freeze fixation has many benefits over conventional chemical fixation. One technique by which rapid freeze-fixation can be achieved, high pressure freezing (HPF), has been shown to enable ice crystal artefact-free freezing and tissue preservation to greater depths (more than 40μm) than other quick-freezing methods. Despite increasingly becoming routine in electron microscopy, the use of HPF for the fixation of inner ear tissue has been limited. Assessment of the quality of preservation showed routine HPF techniques were suitable for preparation of inner ear tissues in a variety of species. Good preservation throughout the depth of sensory epithelia was achievable. Comparison to chemically fixed tissue indicated that fresh frozen preparations exhibited overall superior structural preservation of cells. However, HPF fixation caused characteristic artefacts in stereocilia that suggested poor quality freezing of the actin bundles. The hybrid technique of pre-fixation and high pressure freezing was shown to produce cellular preservation throughout the tissue, similar to that seen in HPF alone. Pre-fixation HPF produced consistent high quality preservation of stereociliary actin bundles. Optimising the preparation of samples with minimal artefact formation allows analysis of the links between ultrastructure and function in inner ear tissues

Assembly of the Auditory Circuitry by a Hox Genetic Network in the Mouse Brainstem

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem

Electronic structure of Pr0.67_{0.67}Ca0.33_{0.33}MnO3_3 near the Fermi level studied by ultraviolet photoelectron and x-ray absorption spectroscopy

We have investigated the temperature-dependent changes in the near-$E$$_F$ occupied and unoccupied states of Pr$_{0.67}$Ca$_{0.33}$MnO$_3$ which shows the presence of ferromagnetic and antiferromagnetic phases. The temperature-dependent changes in the charge and orbital degrees of freedom and associated changes in the Mn 3$d$ - O 2$p$ hybridization result in varied O 2$p$ contributions to the valence band. A quantitative estimate of the charge transfer energy ($E$$_{CT}$) shows a larger value compared to the earlier reported estimates. The charge localization causing the large $E$$_{CT}$ is discussed in terms of different models including the electronic phase separation.Comment: 19 pages, 7 figures, To be published in Phy. Rev.

Molecular Characterisation of Bacterial Wilt Resistance in \u3cem\u3eLolium Multiflorum\u3c/em\u3e Lam.

Italian ryegrass (Lolium multiflorum Lam.), a forage grass of prime importance throughout the world, is adversely affected by the pathogen Xanthomonas translucens pv graminis. Breeding for resistant cultivars is the only practicable means of disease control. However, the inheritance of bacterial wilt resistance is largely unknown. The aim of our research is to elucidate genetic control of bacterial wilt resistance using molecular technologies such as genetic linkage mapping and the analysis of quantitative trait loci (QTL)

Zbtb20 modulates the sequential generation of neuronal layers in developing cortex

BACKGROUND: During corticogenesis, genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities. Transcription factor Zbtb20 has been shown to play a role for hippocampal development but whether it is implicated in mammalian neocortical morphogenesis remains unknown. RESULTS: Here, we report that during embyogenesis transcription factor Zbtb20 has a dynamic spatio-temporal expression pattern in mitotic cortical progenitors through which it modulates the sequential generation of cortical neuronal layer identities. Zbtb20 knock out mice exhibited enhanced populations of early born L6-L4 neuronal subtypes and a dramatic reduction of the late born L3/L2 neurons. This defect was due to a temporal misbalance in the production of earlier versus later born neurons, leading to a progressive diminishing of the progenitor pool for the generation of L3-L2 neurons. Zbtb20 implements these temporal effects in part by binding to promoter of the orphan nuclear receptor CoupTF1/Nr2f1. In addition to its effects exerted in cortical progenitors, the postmitotic expression of Zbtb20 in L3/L2 neurons starting at birth may contribute to their proper differentiation and migration. CONCLUSIONS: Our findings reveal Zbtb20 as a novel temporal regulator for the generation of layer-specific neuronal identities