Efficient polarization squeezing in optical fibers

We report on a novel and efficient source of polarization squeezing using a single pass through an optical fiber. Simply passing this Kerr squeezed beam through a carefully aligned lambda/2 waveplate and splitting it on a polarization beam splitter, we find polarization squeezing of up to 5.1 +/- 0.3 dB. The experimental setup allows for the direct measurement of the squeezing angle.Comment: 4 pages, 4 figure

All-fibre source of amplitude-squeezed light pulses

An all-fibre source of amplitude squeezed solitons utilizing the self-phase modulation in an asymmetric Sagnac interferometer is experimentally demonstrated. The asymmetry of the interferometer is passively controlled by an integrated fibre coupler, allowing for the optimisation of the noise reduction. We have carefully studied the dependence of the amplitude noise on the asymmetry and the power launched into the Sagnac interferometer. Qualitatively, we find good agreement between the experimental results, a semi-classical theory and earlier numerical calculations [Schmitt etl.al., PRL Vol. 81, p.2446, (1998)]. The stability and flexibility of this all-fibre source makes it particularly well suited to applications in quantum information science

Diagnostic study, design and implementation of an integrated model of care in France: a bottom-up process with continuous leadership

<strong>Background: </strong>Sustaining integrated care is difficult, in large part because of problems encountered securing the participation of health care and social service professionals and, in particular, general practitioners (GPs). <p><br /><strong>Purpose: </strong>To present an innovative bottom-up and pragmatic strategy used to implement a new integrated care model in France for community-dwelling elderly people with complex needs.</p><p><br /><strong>Results: </strong>In the first step, a diagnostic study was conducted with face-to-face interviews to gather data on current practices from a sample of health and social stakeholders working with elderly people. In the second step, an integrated care model called Coordination Personnes Agées (COPA) was designed by the same major stakeholders in order to define its detailed characteristics based on the local context. In the third step, the model was implemented in two phases: adoption and maintenance. This strategy was carried out by a continuous and flexible leadership throughout the process, initially with a mixed leadership (clinician and researcher) followed by a double one (clinician and managers of services) in the implementation phase.</p><p><br /><strong>Conclusion: </strong>The implementation of this bottom-up and pragmatic strategy relied on establishing a collaborative dynamic among health and social stakeholders. This enhanced their involvement throughout the implementation phase, particularly among the GPs, and allowed them to support the change practices and services arrangements</p

Permeability of self-affine rough fractures

The permeability of two-dimensional fractures with self-affine fractal roughness is studied via analytic arguments and numerical simulations. The limit where the roughness amplitude is small compared with average fracture aperture is analyzed by a perturbation method, while in the opposite case of narrow aperture, we use heuristic arguments based on lubrication theory. Numerical simulations, using the lattice Boltzmann method, are used to examine the complete range of aperture sizes, and confirm the analytic arguments.Comment: 11 pages, 9 figure

Histone/Protein Deacetylase 11 Targeting Promotes Foxp3+ Treg Function.

Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models. Global HDAC11 deletion had no effect on health or development, and compared to WT controls, Foxp3+ Tregs lacking HDAC11 showed increased suppressive function, and increased expression of Foxp3 and TGF-β. Likewise, compared to WT recipients, conditional deletion of HDAC11 within Tregs led to long-term survival of fully MHC-mismatched cardiac allografts, and prevented development of transplant arteriosclerosis in an MHC class II-mismatched allograft model. The translational significance of HDAC11 targeting was shown by the ability of an HDAC11i to promote long-term allograft allografts in fully MHC-disparate strains. These data are powerful stimuli for the further development and testing of HDAC11-selective pharmacologic inhibitors, and may ultimately provide new therapies for transplantation and autoimmune diseases

Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition

INTRODUCTION: Tau pathology is associated with a number of age-related neurodegenerative disorders. Few treatments have been demonstrated to diminish the impact of tau pathology in mouse models and none are yet effective in humans. Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from cytoplasmic proteins, rather than nuclear histones. Its substrates include tubulin, heat shock protein 90 and cortactin. Tubastatin A is a selective inhibitor of HDAC6. Modification of tau pathology by specific inhibition of HDAC6 presents a potential therapeutic approach in tauopathy. METHODS: We treated rTg4510 mouse models of tau deposition and non-transgenic mice with tubastatin (25 mg/kg) or saline (0.9%) from 5 to 7 months of age. Cognitive behavior analysis, histology and biochemical analysis were applied to access the effect of tubastatin on memory, tau pathology and neurodegeneration (hippocampal volume). RESULTS: We present data showing that tubastatin restored memory function in rTg4510 mice and reversed a hyperactivity phenotype. We further found that tubastatin reduced the levels of total tau, both histologically and by western analysis. Reduction in total tau levels was positively correlated with memory improvement in these mice. However, there was no impact on phosphorylated forms of tau, either by histology or western analysis, nor was there an impact on silver positive inclusions histologically. CONCLUSION: Potential mechanisms by which HDAC6 inhibitors might benefit the rTg4510 mouse include stabilization of microtubules secondary to increased tubulin acetylation, increased degradation of tau secondary to increased acetylation of HSP90 or both. These data support the use of HDAC6 inhibitors as potential therapeutic agents against tau pathology

A pulsed source of continuous variable polarization entanglement

We have experimentally demonstrated polarization entanglement using continuous variables in an ultra-short pulsed laser system at telecommunication wavelengths. Exploiting the Kerr-nonlinearity of a glass fibre we generated a polarization squeezed pulse with S2 the only non-zero Stokes parameter thus S1 and S3 being the conjugate pair. Polarization entanglement was generated by interference of the polarization squeezed field with a vacuum on a 50:50 beam splitter. The two resultant beams exhibit strong quantum noise correlations in S1 and S3. The sum noise signal of S3 was at the respective shot noise level and the difference noise signal of S1 fell 2.9dB below this value

Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER

We describe 280 GHz bolometric detector arrays that instrument the balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to measure the large-scale B-mode polarization of the cosmic microwave background in search of the cosmic-inflation, gravitational-wave signature. 280 GHz channels aid this science goal by constraining the level of B-mode contamination from galactic dust emission. We present the focal plane unit design, which consists of a 16$\times$16 array of conical, corrugated feedhorns coupled to a monolithic detector array fabricated on a 150 mm diameter silicon wafer. Detector arrays are capable of polarimetric sensing via waveguide probe-coupling to a multiplexed array of transition-edge-sensor (TES) bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which in total contains 765 spatial pixels and 1,530 polarization sensitive bolometers. By fabrication and measurement of single feedhorns, we demonstrate 14.7$^{\circ}$ FHWM Gaussian-shaped beams with $<$1% ellipticity in a 30% fractional bandwidth centered at 280 GHz. We present electromagnetic simulations of the detection circuit, which show 94% band-averaged, single-polarization coupling efficiency, 3% reflection and 3% radiative loss. Lastly, we demonstrate a low thermal conductance bolometer, which is well-described by a simple TES model and exhibits an electrical noise equivalent power (NEP) = 2.6 $\times$ 10$^{-17}$ W/$\sqrt{\mathrm{Hz}}$, consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.