Substitute adjustment via recovery of latent variables

The deconfounder was proposed as a method for estimating causal parameters in a context with multiple causes and unobserved confounding. It is based on recovery of a latent variable from the observed causes. We disentangle the causal interpretation from the statistical estimation problem and show that the deconfounder in general estimates adjusted regression target parameters. It does so by outcome regression adjusted for the recovered latent variable termed the substitute. We refer to the general algorithm, stripped of causal assumptions, as substitute adjustment. We give theoretical results to support that substitute adjustment estimates adjusted regression parameters when the regressors are conditionally independent given the latent variable. We also introduce a variant of our substitute adjustment algorithm that estimates an assumption-lean target parameter with minimal model assumptions. We then give finite sample bounds and asymptotic results supporting substitute adjustment estimation in the case where the latent variable takes values in a finite set. A simulation study illustrates finite sample properties of substitute adjustment. Our results support that when the latent variable model of the regressors hold, substitute adjustment is a viable method for adjusted regression

Liquid-infiltrated photonic crystals: Ohmic dissipation and broadening of modes

The pronounced light-matter interactions in photonic crystals make them interesting as opto-fludic "building blocks" for lab-on-a-chip applications. We show how conducting electrolytes cause dissipation and smearing of the density-of-states, thus altering decay dynamics of excited bio-molecules dissolved in the electrolyte. Likewise, we find spatial damping of propagating modes, of the order dB/cm, for naturally occurring electrolytes such as drinking water or physiological salt water.Comment: 9 pages including 2 figure

Sound Transmission Loss of a Sandwich Plate with Adjustable Core Layer Thickness

Compressible Constrained Layer Damping (CCLD) is a novel, semi-active, lightweightcompatible solution for vibration mitigation based on the well-known constrained layer damping principle. The sandwich-like CCLD set-up consists of a base structure, a constraining plate, and a compressible open-cell foam core in between, enabling the adjustment of the structure’s vibration behaviour by changing the core compression using different actuation pressures. The aim of the contribution is to show to what degree, and in which frequency range the acoustic behaviour can be tuned using CCLD. Therefore, the sound transmission loss (TL), as an important vibro-acoustic index, is determined in an acoustic window test stand at different actuation pressures covering a frequency range from 0.5 to 5 kHz. The different actuation pressures applied cause a variation of the core layer thickness (from 0.9 d₀ to 0.3 d₀), but the resulting changes of the stiffness and damping of the overall structure have no significant influence on the TL up to approximately 1 kHz for the analysed CCLD design. Between 1 kHz and 5 kHz, however, the TL can be influenced considerably well by the actuation pressure applied, due to a damping-dominated behaviour around the critical frequenc

Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

International audienceBACKGROUND: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural similarity with mild analgesics. OBJECTIVES AND METHODS: Using cell-based transfection and transduction experiments, mass spectrometry, and organotypic assays together with molecular modeling, we investigated whether inhibition of the PG pathway by known EDCs could be a novel point of endocrine disruption. RESULTS: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis, and this reduction was correlated with a reduced testosterone production. The inhibition of PG synthesis occurred without involvement of canonical PG receptors or the peroxisome proliferator-activated receptors (PPARs), which have previously been described as targets of EDCs. Instead, our results suggest that the compounds may bind directly into the active site of the cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic acid to PG precursors without interfering with the expression of the COX enzymes. A common feature of the PG inhibitory EDCs is the presence of aromatic groups that may stabilize binding in the hydrophobic active site of the COX enzymes. CONCLUSION: Our findings suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades

Liquid-infiltrated photonic crystals - enhanced light-matter interactions for lab-on-a-chip applications

Optical techniques are finding widespread use in analytical chemistry for chemical and bio-chemical analysis. During the past decade, there has been an increasing emphasis on miniaturization of chemical analysis systems and naturally this has stimulated a large effort in integrating microfluidics and optics in lab-on-a-chip microsystems. This development is partly defining the emerging field of optofluidics. Scaling analysis and experiments have demonstrated the advantage of micro-scale devices over their macroscopic counterparts for a number of chemical applications. However, from an optical point of view, miniaturized devices suffer dramatically from the reduced optical path compared to macroscale experiments, e.g. in a cuvette. Obviously, the reduced optical path complicates the application of optical techniques in lab-on-a-chip systems. In this paper we theoretically discuss how a strongly dispersive photonic crystal environment may be used to enhance the light-matter interactions, thus potentially compensating for the reduced optical path in lab-on-a-chip systems. Combining electromagnetic perturbation theory with full-wave electromagnetic simulations we address the prospects for achieving slow-light enhancement of Beer-Lambert-Bouguer absorption, photonic band-gap based refractometry, and high-Q cavity sensing.Comment: Invited paper accepted for the "Optofluidics" special issue to appear in Microfluidics and Nanofluidics (ed. Prof. David Erickson). 11 pages including 8 figure

Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.

Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP

EuroPhenome: a repository for high-throughput mouse phenotyping data.

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies

Homogeneous nonrelativistic geometries as coset spaces

We generalize the coset procedure of homogeneous spacetimes in (pseudo-) Riemannian geometry to non-Lorentzian geometries. These are manifolds endowed with nowhere vanishing invertible vielbeins that transform under local non-Lorentzian tangent space transformations. In particular we focus on nonrelativistic symmetry algebras that give rise to (torsional) Newton-Cartan geometries, for which we demonstrate how the Newton-Cartan metric complex is determined by degenerate co- and contravariant symmetric bilinear forms on the coset. In specific cases we also show the connection of the resulting nonrelativistic coset spacetimes to pseudo-Riemannian cosets via Inonu-Wigner contraction of relativistic algebras as well as null reduction. Our construction is of use for example when considering limits of the AdS/CFT correspondence in which nonrelativistic spacetimes appear as gravitational backgrounds for nonrelativistic string or gravity theories