What Do You Think? Using Expert Opinion to Improve Predictions of Response Propensity Under a Bayesian Framework

Responsive survey designs introduce protocol changes to survey operations based on accumulating paradata. Case-level predictions, including response propensity, can be used to tailor data collection features in pursuit of cost or quality goals. Unfortunately, predictions based only on partial data from the current round of data collection can be biased, leading to ineffective tailoring. Bayesian approaches can provide protection against this bias. Prior beliefs, which are generated from data external to the current survey implementation, contribute information that may be lacking from the partial current data. Those priors are then updated with the accumulating paradata. The elicitation of the prior beliefs, then, is an important characteristic of these approaches. While historical data for the same or a similar survey may be the most natural source for generating priors, eliciting prior beliefs from experienced survey managers may be a reasonable choice for new surveys, or when historical data are not available. Here, we fielded a questionnaire to survey managers, asking about expected attempt-level response rates for different subgroups of cases, and developed prior distributions for attempt-level response propensity model coefficients based on the mean and standard error of their responses. Then, using respondent data from a real survey, we compared the predictions of response propensity when the expert knowledge is incorporated into a prior to those based on a standard method that considers accumulating paradata only, as well as a method that incorporates historical survey data

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

Phase, grain structure, stress, and resistivity of sputter-deposited tungsten films

Sputter-deposited W films with nominal thicknesses between 5 and 180 nm were prepared by varying the base pressure prior to film deposition and by including or not including sputtered SiO(2) encapsulation layers. X-ray and electron diffraction studies showed that single phase, polycrystalline alpha-W could be achieved in as-deposited films as thin as 5 nm. The stress state in the as-deposited films was found to be inhomogeneous. Annealing resulted in stress relaxation and reduction of resistivity for all films, except the thinnest, unencapsulated film, which agglomerated. In-plane film grain sizes measured for a subset of the annealed films with thicknesses between 5 and 180 nm surprisingly showed a near constant value (101-116 nm), independent of film thickness. Thick-film ( \u3e = 120 nm) resistivity values as low as 8.6 mu Omega cm at 301 K were obtained after annealing at 850 degrees C for 2 h. Film resistivities were found to increase with decreasing film thicknesses below 120 nm, even for films which are fully A2 alpha-W with no metastable, A15 beta-W evident

Phase, grain structure, stress, and resistivity of sputter-deposited tungsten films

Sputter-deposited W films with nominal thicknesses between 5 and 180 nm were prepared by varying the base pressure prior to film deposition and by including or not including sputtered SiO(2) encapsulation layers. X-ray and electron diffraction studies showed that single phase, polycrystalline alpha-W could be achieved in as-deposited films as thin as 5 nm. The stress state in the as-deposited films was found to be inhomogeneous. Annealing resulted in stress relaxation and reduction of resistivity for all films, except the thinnest, unencapsulated film, which agglomerated. In-plane film grain sizes measured for a subset of the annealed films with thicknesses between 5 and 180 nm surprisingly showed a near constant value (101-116 nm), independent of film thickness. Thick-film ( \u3e = 120 nm) resistivity values as low as 8.6 mu Omega cm at 301 K were obtained after annealing at 850 degrees C for 2 h. Film resistivities were found to increase with decreasing film thicknesses below 120 nm, even for films which are fully A2 alpha-W with no metastable, A15 beta-W evident

Steady state free radical budgets and ozone photochemistry during TOPSE

A steady state model, constrained by a number of measured quantities, was used to derive peroxy radical levels for the conditions of the Tropospheric Ozone Production about the Spring Equinox (TOPSE) campaign. The analysis is made using data collected aboard the NCAR/NSF C-130 aircraft from February through May 2000 at latitudes from 40° to 85°N, and at altitudes from the surface to 7.6 km. HO2 + RO2 radical concentrations were measured during the experiment, which are compared with model results over the domain of the study showing good agreement on the average. Average measurement/model ratios are 1.04 (σ = 0.73) and 0.96 (σ = 0.52) for the MLB and HLB, respectively. Budgets of total peroxy radical levels as well as of individual free radical members were constructed, which reveal interesting differences compared to studies at lower latitudes. The midlatitude part of the study region is a significant net source of ozone, while the high latitudes constitute a small net sink leading to the hypothesis that transport from the middle latitudes can explain the observed increase in ozone in the high latitudes. Radical reservoir species concentrations are modeled and compared with the observations. For most conditions, the model does a good job of reproducing the formaldehyde observations, but the peroxide observations are significantly less than steady state for this study. Photostationary state (PSS) derived total peroxy radical levels and NO/NO2ratios are compared with the measurements and the model; PSS-derived results are higher than observations or the steady state model at low NO concentrations

JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length

c-Jun NH2-terminal kinases (JNKs) are essential during brain development, when they regulate morphogenic changes involving cell movement and migration. In the adult, JNK determines neuronal cytoarchitecture. To help uncover the molecular effectors for JNKs in these events, we affinity purified JNK-interacting proteins from brain. This revealed that the stathmin family microtubule-destabilizing proteins SCG10, SCLIP, RB3, and RB3′ interact tightly with JNK. Furthermore, SCG10 is also phosphorylated by JNK in vivo on sites that regulate its microtubule depolymerizing activity, serines 62 and 73. SCG10-S73 phosphorylation is significantly decreased in JNK1−/− cortex, indicating that JNK1 phosphorylates SCG10 in developing forebrain. JNK phosphorylation of SCG10 determines axodendritic length in cerebrocortical cultures, and JNK site–phosphorylated SCG10 colocalizes with active JNK in embryonic brain regions undergoing neurite elongation and migration. We demonstrate that inhibition of cytoplasmic JNK and expression of SCG10-62A/73A both inhibited fluorescent tubulin recovery after photobleaching. These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development

Ozone depletion events observed in the high latitude surface layer during the TOPSE aircraft program

During the Tropospheric Ozone Production about the Spring Equinox (TOPSE) aircraft program, ozone depletion events (ODEs) in the high latitude surface layer were investigated using lidar and in situ instruments. Flight legs of 100 km or longer distance were flown 32 times at 30 m altitude over a variety of regions north of 58° between early February and late May 2000. ODEs were found on each flight over the Arctic Ocean but their occurrence was rare at more southern latitudes. However, large area events with depletion to over 2 km altitude in one case were found as far south as Baffin Bay and Hudson Bay and as late as 22 May. There is good evidence that these more southern events did not form in situ but were the result of export of ozone-depleted air from the surface layer of the Arctic Ocean. Surprisingly, relatively intact transport of ODEs occurred over distances of 900–2000 km and in some cases over rough terrain. Accumulation of constituents in the frozen surface over the dark winter period cannot be a strong prerequisite of ozone depletion since latitudes south of the Arctic Ocean would also experience a long dark period. Some process unique to the Arctic Ocean surface or its coastal regions remains unidentified for the release of ozone-depleting halogens. There was no correspondence between coarse surface features such as solid ice/snow, open leads, or polynyas with the occurrence of or intensity of ozone depletion over the Arctic or subarctic regions. Depletion events also occurred in the absence of long-range transport of relatively fresh “pollution” within the high latitude surface layer, at least in spring 2000. Direct measurements of halogen radicals were not made. However, the flights do provide detailed information on the vertical structure of the surface layer and, during the constant 30 m altitude legs, measurements of a variety of constituents including hydroxyl and peroxy radicals. A summary of the behavior of these constituents is made. The measurements were consistent with a source of formaldehyde from the snow/ice surface. Median NOx in the surface layer was 15 pptv or less, suggesting that surface emissions were substantially converted to reservoir constituents by 30 m altitude and that ozone production rates were small (0.15–1.5 ppbv/d) at this altitude. Peroxyacetylnitrate (PAN) was by far the major constituent of NOy in the surface layer independent of the ozone mixing ratio