Strong and Tunable Nonlinear Optomechanical Coupling in a Low-Loss System

A major goal in optomechanics is to observe and control quantum behavior in a system consisting of a mechanical resonator coupled to an optical cavity. Work towards this goal has focused on increasing the strength of the coupling between the mechanical and optical degrees of freedom; however, the form of this coupling is crucial in determining which phenomena can be observed in such a system. Here we demonstrate that avoided crossings in the spectrum of an optical cavity containing a flexible dielectric membrane allow us to realize several different forms of the optomechanical coupling. These include cavity detunings that are (to lowest order) linear, quadratic, or quartic in the membrane's displacement, and a cavity finesse that is linear in (or independent of) the membrane's displacement. All these couplings are realized in a single device with extremely low optical loss and can be tuned over a wide range in situ; in particular, we find that the quadratic coupling can be increased three orders of magnitude beyond previous devices. As a result of these advances, the device presented here should be capable of demonstrating the quantization of the membrane's mechanical energy.Comment: 12 pages, 4 figures, 1 tabl

A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana

Identifying natural allelic variation that underlies quantitative trait variation remains a fundamental problem in genetics. Most studies have employed either simple synthetic populations with restricted allelic variation or performed association mapping on a sample of naturally occurring haplotypes. Both of these approaches have some limitations, therefore alternative resources for the genetic dissection of complex traits continue to be sought. Here we describe one such alternative, the Multiparent Advanced Generation Inter-Cross (MAGIC). This approach is expected to improve the precision with which QTL can be mapped, improving the outlook for QTL cloning. Here, we present the first panel of MAGIC lines developed: a set of 527 recombinant inbred lines (RILs) descended from a heterogeneous stock of 19 intermated accessions of the plant Arabidopsis thaliana. These lines and the 19 founders were genotyped with 1,260 single nucleotide polymorphisms and phenotyped for development-related traits. Analytical methods were developed to fine-map quantitative trait loci (QTL) in the MAGIC lines by reconstructing the genome of each line as a mosaic of the founders. We show by simulation that QTL explaining 10% of the phenotypic variance will be detected in most situations with an average mapping error of about 300 kb, and that if the number of lines were doubled the mapping error would be under 200 kb. We also show how the power to detect a QTL and the mapping accuracy vary, depending on QTL location. We demonstrate the utility of this new mapping population by mapping several known QTL with high precision and by finding novel QTL for germination data and bolting time. Our results provide strong support for similar ongoing efforts to produce MAGIC lines in other organisms

Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders

Turner syndrome (TS) is one of the most common sex chromosome abnormalities. Affected individuals often show a unique pattern of cognitive strengths and weaknesses and are at increased risk for a number of other neurodevelopmental conditions, many of which are more common in typical males than typical females (e.g., autism and attention-deficit hyperactivity disorder). This phenotype may reflect gonadal steroid deficiency, haploinsufficiency of X chromosome genes, failure to express parentally imprinted genes, and the uncovering of X chromosome mutations. Understanding the contribution of these different mechanisms to outcome has the potential to improve clinical care for individuals with TS and to better our understanding of the differential vulnerability to and expression of neurodevelopmental disorders in males and females. In this paper, we review what is currently known about cognition and brain development in individuals with TS, discuss underlying mechanisms and their relevance to understanding male-biased neurodevelopmental conditions, and suggest directions for future research

The impact of reproductive issues on preferences of women with relapsing multiple sclerosis for disease modifying treatments

Background Relapsing–remitting multiple sclerosis (RRMS) is an incurable disease characterised by relapses (periods of function loss) followed by full or partial recovery, and potential permanent disability over time. Many disease-modifying treatments (DMTs) exist that help reduce relapses and slow disease progression. Most are contraindicated during conception/pregnancy and some require a discontinuation period before trying to conceive. Although around three-quarters of people with RRMS are women, there is limited knowledge about how reproductive issues impact DMT preference. Objective The aim of this study was to measure the preferences for DMTs of women with RRMS who are considering pregnancy. Design An online discrete choice experiment (DCE). Methods Participants chose between two hypothetical DMTs characterised by a set of attributes, then indicated if they preferred their choice to no treatment. Attributes were identified from interviews and focus groups with people with RRMS and MS professionals, as well as literature reviews, and included the probability of problems with pregnancy, discontinuation of DMTs, and breastfeeding safety. In each DCE task, participants were asked to imagine making decisions in three scenarios: now; when trying to conceive; and when pregnant. Analysis Two mixed logit models were estimated, one to assess the statistical significance between scenarios and one in maximum acceptable risk space to allow comparison of the magnitudes of parameters between scenarios. Sample Women with RRMS who were considering having a child in the future, recruited from a UK MS patient register. Results Sixty respondents completed the survey. Participants preferred no treatment in 12.6% of choices in the ‘now’ scenario, rising significantly to 37.6% in the ‘trying to conceive’ scenario and 60.3% in the ‘pregnant’ scenario (Kruskal–Wallis p < 0.001). This pattern corresponds with results from models that included a no-treatment alternative-specific constant (ASC) capturing differences between taking and not taking a DMT not specified by the attributes. The ASC was lower in the trying to conceive scenario than in the now scenario, and lower still in the pregnant scenario, indicating an intrinsic preference for no treatment. Participants also placed relatively less preference on reducing relapses and avoiding disease progression in the trying to conceive and pregnant scenarios compared with a lower risk of problems with pregnancy. In the trying to conceive scenario, participants’ preference for treatments with shorter washout periods increased. Conclusion Women with RRMS considering having a child prefer DMTs with more favourable reproduction-related attributes, even when not trying to conceive. Reproductive issues also influenced preferences for DMT attributes not directly related to pregnancy, with preferences dependent on the life circumstances in which choices were made. The design of the DCE highlights the benefits of considering the scenario in which participants make choices, as they may change over time

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA