2,212 research outputs found
Likelihood Ratio Test process for Quantitative Trait Locus detection
International audienceWe consider the likelihood ratio test (LRT) process related to the test of the absence of QTL (a QTL denotes a quantitative trait locus, i.e. a gene with quantitative effect on a trait) on the interval [0,T] representing a chromosome. The observation is the trait and the composition of the genome at some locations called ''markers''. We give the asymptotic distribution of this LRT process under the null hypothesis that there is no QTL on [0,T] and under local alternatives with a QTL at t* on [0,T]. We show that the LRT is asymptotically the square of some Gaussian process. We give a description of this process as an '' non-linear interpolated and normalized process ''. We propose a simple method to calculate the maximum of the LRT process using only statistics on markers and their ratio. This gives a new method to calculate thresholds for QTL detection
Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort
\ua9 The Author(s) 2017.Changes in the mean and variance of gene expression with age have consequences for healthy aging and disease development. Age-dependent changes in phenotypic variance have been associated with a decline in regulatory functions leading to increase in disease risk. Here, we investigate age-related mean and variance changes in gene expression measured by RNA-seq of fat, skin, whole blood and derived lymphoblastoid cell lines (LCLs) expression from 855 adult female twins. We see evidence of up to 60% of age effects on transcription levels shared across tissues, and 47% of those on splicing. Using gene expression variance and discordance between genetically identical MZ twin pairs, we identify 137 genes with age-related changes in variance and 42 genes with age-related discordance between co-twins; implying the latter are driven by environmental effects. We identify four eQTLs whose effect on expression is age-dependent (FDR 5%). Combined, these results show a complicated mix of environmental and genetically driven changes in expression with age. Using the twin structure in our data, we show that additive genetic effects explain considerably more of the variance in gene expression than aging, but less that other environmental factors, potentially explaining why reliable expression-derived biomarkers for healthy-aging have proved elusive compared with those derived from methylation
Brownian bridges to submanifolds
We introduce and study Brownian bridges to submanifolds. Our method involves
proving a general formula for the integral over a submanifold of the minimal
heat kernel on a complete Riemannian manifold. We use the formula to derive
lower bounds, an asymptotic relation and derivative estimates. We also see a
connection to hypersurface local time. This work is motivated by the desire to
extend the analysis of path and loop spaces to measures on paths which
terminate on a submanifold
Effect of substrate thermal resistance on space-domain microchannel
In recent years, Fluorescent Melting Curve Analysis (FMCA) has become an almost ubiquitous feature of commercial quantitative PCR (qPCR) thermal cyclers. Here a micro-fluidic device is presented capable of performing FMCA within a microchannel. The device consists of modular thermally conductive blocks which can sandwich a microfluidic substrate. Opposing ends of the blocks are held at differing temperatures and a linear thermal gradient is generated along the microfluidic channel. Fluorescent measurements taken from a sample as it passes along the micro-fluidic channel permits fluorescent melting curves to be generated. In this study we measure DNA melting temperature from two plasmid fragments. The effects of flow velocity and ramp-rate are investigated, and measured melting curves are compared to those acquired from a commercially available PCR thermocycler
Spectrin-beta 2 facilitates the selective accumulation of GABAA receptors at somatodendritic synapses
Fast synaptic inhibition is dependent on targeting specific GABAAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABAARs are typically assembled from α1-3, β and γ subunits. Here, we isolate distinct GABAARs from the brain and interrogate their composition using quantitative proteomics. We show that α2-containing receptors co-assemble with α1 subunits, whereas α1 receptors can form GABAARs with α1 as the sole α subunit. We demonstrate that α1 and α2 subunit-containing receptors co-purify with distinct spectrin isoforms; cytoskeletal proteins that link transmembrane proteins to the cytoskeleton. β2-spectrin was preferentially associated with α1-containing GABAARs at dendritic synapses, while β4-spectrin was associated with α2-containing GABAARs at AIS synapses. Ablating β2-spectrin expression reduced dendritic and AIS synapses containing α1 but increased the number of synapses containing α2, which altered phasic inhibition. Thus, we demonstrate a role for spectrins in the synapse-specific targeting of GABAARs, determining the efficacy of fast neuronal inhibition
Seeing Tree Structure from Vibration
Humans recognize object structure from both their appearance and motion;
often, motion helps to resolve ambiguities in object structure that arise when
we observe object appearance only. There are particular scenarios, however,
where neither appearance nor spatial-temporal motion signals are informative:
occluding twigs may look connected and have almost identical movements, though
they belong to different, possibly disconnected branches. We propose to tackle
this problem through spectrum analysis of motion signals, because vibrations of
disconnected branches, though visually similar, often have distinctive natural
frequencies. We propose a novel formulation of tree structure based on a
physics-based link model, and validate its effectiveness by theoretical
analysis, numerical simulation, and empirical experiments. With this
formulation, we use nonparametric Bayesian inference to reconstruct tree
structure from both spectral vibration signals and appearance cues. Our model
performs well in recognizing hierarchical tree structure from real-world videos
of trees and vessels.Comment: ECCV 2018. The first two authors contributed equally to this work.
Project page: http://tree.csail.mit.edu
Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear
We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome
Galaxy and Mass Assembly (GAMA): Morphological transformation of galaxies across the green valley
We explore constraints on the joint photometric and morphological evolution of typical low redshift galaxies as they move from the blue cloud through the green valley and onto the red sequence. We select GAMA survey galaxies with and classified according to their intrinsic colour. From single component S\'ersic fits, we find that the stellar mass-sensitive band profiles of red and green galaxy populations are very similar, while band profiles indicate more disk-like morphologies for the green galaxies: apparent (optical) morphological differences arise primarily from radial mass-to-light ratio variations. Two-component fits show that most green galaxies have significant bulge and disk components and that the blue to red evolution is driven by colour change in the disk. Together, these strongly suggest that galaxies evolve from blue to red through secular disk fading and that a strong bulge is present prior to any decline in star formation. The relative abundance of the green population implies a typical timescale for traversing the green valley ~Gyr and is independent of environment, unlike that of the red and blue populations. While environment likely plays a r\^ole in triggering the passage across the green valley, it appears to have little effect on time taken. These results are consistent with a green valley population dominated by (early type) disk galaxies that are insufficiently supplied with gas to maintain previous levels of disk star formation, eventually attaining passive colours. No single event is needed quench their star formation
Galaxy and Mass Assembly (GAMA): Accurate number densities and environments of massive ultracompact galaxies at 0.02 < z < 0.3
Massive Ultracompact Galaxies (MUGs) are common at z=2-3, but very rare in the nearby Universe. Simulations predict that the few surviving MUGs should reside in galaxy clusters, whose large relative velocities prevent them from merging, thus maintaining their original properties (namely stellar populations, masses, sizes and dynamical state). We take advantage of the high-completeness, large-area spectroscopic GAMA survey, complementing it with deeper imaging from the KiDS and VIKING surveys. We find a set of 22 bona-fide MUGs, defined as having high stellar mass (>8x10^10 M_Sun) and compact size (R_e ~ 10^10 M_Sun Kpc^-2). Interestingly, a large fraction feature close companions -- at least in projection -- suggesting that many (but not all) live in the central regions of groups. Halo masses show these galaxies inhabit average-mass groups. As MUGs are found to be almost equally distributed among environments of different masses, their relative fraction is higher in more massive overdensities, matching the expectations that some of these galaxies fell in these regions at early times. However, there must be another channel leading some of these galaxies to an abnormally low merger history because our sample shows a number of objects that do not inhabit particularly dense environments. (abridged
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