Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice

Elastic fibers provide tissues with elasticity which is critical to the function of arteries, lungs, skin, and other dynamic organs. Loss of elasticity is a major contributing factor in aging and diseases. However, the mechanism of elastic fiber development and assembly is poorly understood. Here, we show that lack of fibulin-4, an extracellular matrix molecule, abolishes elastogenesis. fibulin-4(−/−) mice generated by gene targeting exhibited severe lung and vascular defects including emphysema, artery tortuosity, irregularity, aneurysm, rupture, and resulting hemorrhages. All the homozygous mice died perinatally. The earliest abnormality noted was a uniformly narrowing of the descending aorta in fibulin-4(−/−) embryos at embryonic day 12.5 (E12.5). Aorta tortuosity and irregularity became noticeable at E15.5. Histological analysis demonstrated that fibulin-4(−/−) mice do not develop intact elastic fibers but contain irregular elastin aggregates. Electron microscopy revealed that the elastin aggregates are highly unusual in that they contain evenly distributed rod-like filaments, in contrast to the amorphous appearance of normal elastic fibers. Desmosine analysis indicated that elastin cross-links in fibulin-4(−/−) tissues were largely diminished. However, expression of tropoelastin or lysyl oxidase mRNA was unaffected in fibulin-4(−/−) mice. In addition, fibulin-4 strongly interacts with tropoelastin and colocalizes with elastic fibers in culture. These results demonstrate that fibulin-4 plays an irreplaceable role in elastogenesis

Optimality Driven Nearest Centroid Classification from Genomic Data

Nearest-centroid classifiers have recently been successfully employed in high-dimensional applications, such as in genomics. A necessary step when building a classifier for high-dimensional data is feature selection. Feature selection is frequently carried out by computing univariate scores for each feature individually, without consideration for how a subset of features performs as a whole. We introduce a new feature selection approach for high-dimensional nearest centroid classifiers that instead is based on the theoretically optimal choice of a given number of features, which we determine directly here. This allows us to develop a new greedy algorithm to estimate this optimal nearest-centroid classifier with a given number of features. In addition, whereas the centroids are usually formed from maximum likelihood estimates, we investigate the applicability of high-dimensional shrinkage estimates of centroids. We apply the proposed method to clinical classification based on gene-expression microarrays, demonstrating that the proposed method can outperform existing nearest centroid classifiers

Isospin Multiplet Structure in Ultra--Heavy Fermion Bound States

The coupled Bethe--Salpeter bound state equations for a $Q\bar Q$ system, where $Q=(U,D)$ is a degenerate, fourth generation, super--heavy quark doublet, are solved in several ladder approximation models. The exchanges of gluon, Higgs and Goldstone modes in the standard model are calculated in the ultra--heavy quark limit where weak $\gamma, W^\pm$ and $Z^0$ contributions are negligible. A natural $I=0$ and $I=1$ multiplet pattern is found, with large splittings occuring between the different weak iso--spin states when $M_Q$, the quark masses, are larger than values in the range $0.4 TeV<M_Q<0.8 TeV$, depending on which model is used. Consideration of ultra--heavy quark lifetime constraints and $U-D$ mass splitting constraints are reviewed to establish the plausibility of lifetime and mass degeneracy requirements assumed for this paper.Comment: 20 pages, 7 figures (hard copy available upon request), report# KU-HEP-93-2

The u'g'r'i'z' Standard Star Network

We present the 158 standard stars that define the u'g'r'i'z' photometric system. These stars form the basis for the photometric calibration of the Sloan Digital Sky Survey (SDSS). The defining instrument system and filters, the observing process, the reduction techniques, and the software used to create the stellar network are all described. We briefly discuss the history of the star selection process, the derivation of a set of transformation equations for the UBVRcIc system, and plans for future work.Comment: References to URLs in paper have been updated to reflect moved website. Accepted by AJ. 50 pages, including 20 pages of text, 9 tables, and 15 figures. Plain ASCII text versions of Tables 8 and 9 can be found at http://home.fnal.gov/~dtucker/ugriz/index.html (new URL

Sharing design definitions across product life cycles

The research reported in this paper explored the feasibility of embedding multiple design structures into design definitions with a view of sharing design definitions across product life cycles. Two separate case studies using (a) lattice theory and (b) a qualitative data analysis (QDA) software tool were used to illustrate the benefits of embedding. In the first case study, of a robotic arm assembly, lattices in the form of partially ordered sets are used to embed multiple design structures into a given design definition. A software prototype has been built that allows a design bill of materials (BoM) to be extracted from a STEP AP214 file and translated into a lattice that is visualized as a Hasse diagram. This lattice is a sub-lattice of a complete lattice that includes all possible BoM structures for the given collection of component parts in the assembly. New BoM design structures can be defined by selecting the required nodes in the complete lattice and alternative product definitions are then exported as new STEP files. The second case study introduces a collision avoidance robot with associated design structures. It is used to illustrate management of design information using a current technique, design structure matrix (DSM), and compared with how embedding using QDA has the potential to support the establishment of relationships between design structures. Results from these case studies demonstrate that it is feasible to use lattice theory as an underlying formalism and QDA as a means for sharing design definitions

Re-examining the effects of verbal instructional type on early stage motor learning

The present study investigated the differential effects of analogy and explicit instructions on early stage motor learning and movement in a modified high jump task. Participants were randomly assigned to one of three experimental conditions: analogy, explicit light (reduced informational load), or traditional explicit (large informational load). During the two-day learning phase, participants learned a novel high jump technique based on the ‘scissors’ style using the instructions for their respective conditions. For the single-day testing phase, participants completed both a retention test and task-relevant pressure test, the latter of which featured a rising high-jump-bar pressure manipulation. Although analogy learners demonstrated slightly more efficient technique and reported fewer technical rules on average, the differences between the conditions were not statistically significant. There were, however, significant differences in joint variability with respect to instructional type, as variability was lowest for the analogy condition during both the learning and testing phases, and as a function of block, as joint variability decreased for all conditions during the learning phase. Findings suggest that reducing the informational volume of explicit instructions may mitigate the deleterious effects on performance previously associated with explicit learning in the literature

Association between Hypertension and Retinal Vascular Features in Ultra-Widefield Fundus Imaging

Objective: Changes to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.Methods: We retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal-annular arteriole:venule ratio (NA-AVR), a novel combined parameter.Results: Left and right eyes were analysed from 440 participants (aged 50-59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).Conclusions: Semiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.</p

Impaired perception of facial motion in autism spectrum disorder

Copyright: © 2014 O’Brien et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Facial motion is a special type of biological motion that transmits cues for socio-emotional communication and enables the discrimination of properties such as gender and identity. We used animated average faces to examine the ability of adults with autism spectrum disorders (ASD) to perceive facial motion. Participants completed increasingly difficult tasks involving the discrimination of (1) sequences of facial motion, (2) the identity of individuals based on their facial motion and (3) the gender of individuals. Stimuli were presented in both upright and upside-down orientations to test for the difference in inversion effects often found when comparing ASD with controls in face perception. The ASD group’s performance was impaired relative to the control group in all three tasks and unlike the control group, the individuals with ASD failed to show an inversion effect. These results point to a deficit in facial biological motion processing in people with autism, which we suggest is linked to deficits in lower level motion processing we have previously reported

Principles for the definition of design structures

Different kinds of design structure are created and used in engineering design and development processes. Function structures, design grammars and bills of materials are common examples. However, there is a lack of clarity regarding distinctions and similarities between different kinds of structure and systematic ways to articulate them. This paper brings together research on product structuring and shape computation to inform the specification of principles for the definition of design structures. The principles draw together findings reported in the computational geometry and product definition literature with research from a range of companies and industry sectors that encompasses enterprise and process structures. The potential value of the principles to computer integrated manufacturing and through-life support is demonstrated through application to four case studies

Galaxy Clustering in Early SDSS Redshift Data

We present the first measurements of clustering in the Sloan Digital Sky Survey (SDSS) galaxy redshift survey. Our sample consists of 29,300 galaxies with redshifts 5,700 km/s < cz < 39,000 km/s, distributed in several long but narrow (2.5-5 degree) segments, covering 690 square degrees. For the full, flux-limited sample, the redshift-space correlation length is approximately 8 Mpc/h. The two-dimensional correlation function \xi(r_p,\pi) shows clear signatures of both the small-scale, ``fingers-of-God'' distortion caused by velocity dispersions in collapsed objects and the large-scale compression caused by coherent flows, though the latter cannot be measured with high precision in the present sample. The inferred real-space correlation function is well described by a power law, \xi(r)=(r/6.1+/-0.2 Mpc/h)^{-1.75+/-0.03}, for 0.1 Mpc/h < r < 16 Mpc/h. The galaxy pairwise velocity dispersion is \sigma_{12} ~ 600+/-100 km/s for projected separations 0.15 Mpc/h < r_p < 5 Mpc/h. When we divide the sample by color, the red galaxies exhibit a stronger and steeper real-space correlation function and a higher pairwise velocity dispersion than do the blue galaxies. The relative behavior of subsamples defined by high/low profile concentration or high/low surface brightness is qualitatively similar to that of the red/blue subsamples. Our most striking result is a clear measurement of scale-independent luminosity bias at r < 10 Mpc/h: subsamples with absolute magnitude ranges centered on M_*-1.5, M_*, and M_*+1.5 have real-space correlation functions that are parallel power laws of slope ~ -1.8 with correlation lengths of approximately 7.4 Mpc/h, 6.3 Mpc/h, and 4.7 Mpc/h, respectively.Comment: 51 pages, 18 figures. Replaced to match accepted ApJ versio