Optical measurements of phase steps in segmented mirrors - fundamental precision limits

Phase steps are an important type of wavefront aberrations generated by large telescopes with segmented mirrors. In a closed-loop correction cycle these phase steps have to be measured with the highest possible precision using natural reference stars, that is with a small number of photons. In this paper the classical Fisher information of statistics is used for calculating the Cramer-Rao bound, which determines the limit to the precision with which the height of the steps can be estimated in an unbiased fashion with a given number of photons and a given measuring device. Four types of measurement devices are discussed: a Shack-Hartmann sensor with one small cylindrical lenslet covering a sub-aperture centred over a border, a modified Mach-Zehnder interferometer, a Foucault test, and a curvature sensor. The Cramer-Rao bound is calculated for all sensors under ideal conditions, that is narrowband measurements without additional noise or disturbances apart from the photon shot noise. This limit is compared with the ultimate quantum statistical limit for the estimate of such a step which is independent of the measuring device. For the Shack-Hartmann sensor, the effects on the Cramer-Rao bound of broadband measurements, finite sampling, and disturbances such as atmospheric seeing and detector readout noise are also investigated. The methods presented here can be used to compare the precision limits of various devices for measuring phase steps and for optimising the parameters of the devices. Under ideal conditions the Shack-Hartmann and the Foucault devices nearly attain the ultimate quantum statistical limits, whereas the Mach-Zehnder and the curvature devices each require approximately twenty times as many photons in order to reach the same precision.Comment: 23 pages, 19 figures, to be submitted to Journal of Modern Optic

The response of a neutral atom to a strong laser field probed by transient absorption near the ionisation threshold

We present transient absorption spectra of an extreme ultraviolet attosecond pulse train in helium dressed by an 800 nm laser field with intensity ranging from $2times10^{12}$ W/cm$^2$ to $2times10^{14}$ W/cm$^2$. The energy range probed spans 16-42 eV, straddling the first ionisation energy of helium (24.59 eV). By changing the relative polarisation of the dressing field with respect to the attosecond pulse train polarisation we observe a large change in the modulation of the absorption reflecting the vectorial response to the dressing field. With parallel polarized dressing and probing fields, we observe significant modulations with periods of one half and one quarter of the dressing field period. With perpendicularly polarized dressing and probing fields, the modulations of the harmonics above the ionisation threshold are significantly suppressed. A full-dimensionality solution of the single-atom time-dependent Schr odinger equation obtained using the recently developed ab-initio time-dependent B-spline ADC method reproduce some of our observations

Three-Dimensional Spectral-Domain Optical Coherence Tomography Data Analysis for Glaucoma Detection

Purpose: To develop a new three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) data analysis method using a machine learning technique based on variable-size super pixel segmentation that efficiently utilizes full 3D dataset to improve the discrimination between early glaucomatous and healthy eyes. Methods: 192 eyes of 96 subjects (44 healthy, 59 glaucoma suspect and 89 glaucomatous eyes) were scanned with SD-OCT. Each SD-OCT cube dataset was first converted into 2D feature map based on retinal nerve fiber layer (RNFL) segmentation and then divided into various number of super pixels. Unlike the conventional super pixel having a fixed number of points, this newly developed variable-size super pixel is defined as a cluster of homogeneous adjacent pixels with variable size, shape and number. Features of super pixel map were extracted and used as inputs to machine classifier (LogitBoost adaptive boosting) to automatically identify diseased eyes. For discriminating performance assessment, area under the curve (AUC) of the receiver operating characteristics of the machine classifier outputs were compared with the conventional circumpapillary RNFL (cpRNFL) thickness measurements. Results: The super pixel analysis showed statistically significantly higher AUC than the cpRNFL (0.855 vs. 0.707, respectively, p = 0.031, Jackknife test) when glaucoma suspects were discriminated from healthy, while no significant difference was found when confirmed glaucoma eyes were discriminated from healthy eyes. Conclusions: A novel 3D OCT analysis technique performed at least as well as the cpRNFL in glaucoma discrimination and even better at glaucoma suspect discrimination. This new method has the potential to improve early detection of glaucomatous damage. © 2013 Xu et al

The Complete Star Formation History of the Universe

The determination of the star-formation history of the Universe is a key goal of modern cosmology, as it is crucial to our understanding of how structure in the Universe forms and evolves. A picture has built up over recent years, piece-by-piece, by observing young stars in distant galaxies at different times in the past. These studies indicated that the stellar birthrate peaked some 8 billion years ago, and then declined by a factor of around ten to its present value. Here we report on a new study which obtains the complete star formation history by analysing the fossil record of the stellar populations of 96545 nearby galaxies. Broadly, our results support those derived from high-redshift galaxies elsewhere in the Universe. We find, however, that the peak of star formation was more recent - around 5 billion years ago. Our study also shows that the bigger the stellar mass of the galaxy, the earlier the stars were formed. This striking result indicates a very different formation history for high- and low-mass formation.Comment: Accepted by Nature. Press embargo until publishe

Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis

The Fc gamma receptors have been shown to play important roles in the initiation and regulation of many immunological and inflammatory processes and to amplify and refine the immune response to an infection. We have investigated the hypothesis that polymorphism within the FCGR genetic locus is associated with giant cell arteritis (GCA). Biallelic polymorphisms in FCGR2A, FCGR3A, FCGR3B and FCGR2B were examined for association with biopsy-proven GCA (n = 85) and healthy ethnically matched controls (n = 132) in a well-characterised cohort from Lugo, Spain. Haplotype frequencies and linkage disequilibrium (D') were estimated across the FCGR locus and a model-free analysis performed to determine association with GCA. There was a significant association between FCGR2A-131RR homozygosity (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.12 to 3.77, P = 0.02, compared with all others) and carriage of FCGR3A-158F (OR 3.09, 95% CI 1.10 to 8.64, P = 0.03, compared with non-carriers) with susceptibility to GCA. FCGR haplotypes were examined to refine the extent of the association. The haplotype showing the strongest association with GCA susceptibility was the FCGR2A-FCGR3A 131R-158F haplotype (OR 2.84, P = 0.01 for homozygotes compared with all others). There was evidence of a multiplicative joint effect between homozygosity for FCGR2A-131R and HLA-DRB1*04 positivity, consistent with both of these two genetic factors contributing to the risk of disease. The risk of GCA in HLA-DRB1*04 positive individuals homozygous for the FCGR2A-131R allele is increased almost six-fold compared with those with other FCGR2A genotypes who are HLA-DRB1*04 negative. We have demonstrated that FCGR2A may contribute to the 'susceptibility' of GCA in this Spanish population. The increased association observed with a FCGR2A-FCGR3A haplotype suggests the presence of additional genetic polymorphisms in linkage disequilibrium with this haplotype that may contribute to disease susceptibility. These findings may ultimately provide new insights into disease pathogenesis

LINC complex-Lisl interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration

Cancer cells' ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD