A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

Introduction:Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives.Methods:Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification.Results:All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.Conclusions:IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein

Effects of meteorological and land surface modeling uncertainty on errors in winegrape ET calculated with SIMS

Characterization of model errors is important when applying satellite-driven evapotranspiration (ET) models to water resource management problems. This study examines how uncertainty in meteorological forcing data and land surface modeling propagate through to errors in final ET data calculated using the Satellite Irrigation Management Support (SIMS) model, a computationally efficient ET model driven with satellite surface reflectance values. The model is applied to three instrumented winegrape vineyards over the 2017-2020 time period and the spatial and temporal variation in errors are analyzed. We illustrate how meteorological data inputs can introduce biases that vary in space and at seasonal timescales, but that can persist from year to year. We also observe that errors in SIMS estimates of land surface conductance can have a particularly strong dependence on time of year. Overall, meteorological inputs introduced RMSE of 0.33-0.65 mm/day (7-27%) across sites, while SIMS introduced RMSE of 0.55-0.83 mm/day (19-24%). The relative error contribution from meteorological inputs versus SIMS varied across sites; errors from SIMS were larger at one site, errors from meteorological inputs were larger at a second site, and the error contributions were of equal magnitude at the third site. The similar magnitude of error contributions is significant given that many satellite-driven ET models differ in their approaches to estimating land surface conductance, but often rely on similar or identical meteorological forcing data. The finding is particularly notable given that SIMS makes assumptions about the land surface (no soil evaporation or plant water stress) that do not always hold in practice. The results of this study show that improving SIMS by eliminating these assumptions would result in meteorological inputs dominating the error budget of the model on the whole. This finding underscores the need for further work on characterizing spatial uncertainty in the meteorological forcing of ET

When social movements fail or succeed: social psychological consequences of a collective action’s outcome

Collective actions occur all around the world and, in the last few years, even more frequently. Previous literature has mainly focused on the antecedents of collective actions, but less attention has been given to the consequences of participating in collective action. Moreover, it is still an open question how the consequences of collective action might differ, depending on whether the actions are perceived to succeed or fail. In two studies we seek to address this gap using innovative experimental studies. In Study 1 (N = 368) we manipulated the perceptions of success and failure of a collective action in the context of a real social movement, the Chilean student movement from last decade. In Study 2 (N = 169), in addition to manipulating the outcome, we manipulated actual participation, using a mock environmental organization aiming to create awareness in authorities, to test the causal effect of both participation and success/failure on empowerment, group efficacy, and intentions of future involvement in normative and non-normative collective actions. Results show that current and past participation predict overall participation in the future, however, in Study 2 the manipulated participation was associated with having less intentions of participating in the future. In both studies, perception of success increases group efficacy. In Study 1, we found that when facing failure, participants increase their willingness to participate more in the future as opposed to non-participants that actually decrease theirs. In Study 2, however, failure increases the perception of efficacy for those with a history of non-normative participation. Altogether these results highlight the moderating role of the outcome of collective action to understand the effect of participation on future participation. We discuss these results in light of the methodological innovation and the real world setting in which our studies were conducted

Assessing Domestic Heat Storage Requirements for Energy Flexibility Over Varying Timescales

This paper explores the feasibility of storing heat in an encapsulated store to support thermal load shifting over three timescales: diurnal, weekly and seasonal. A building simulation tool was used to calculate the space heating and hot water demands for four common UK housing types and a range of operating conditions. A custom sizing methodology calculated the capacities of storage required to fully meet the heat demands over the three timescales. Corresponding storage volumes were calculated for a range of heat storage materials deemed suitable for storing heat within a dwelling, either in a tank or as an integral part of the building fabric: hot water, concrete, high-temperature magnetite blocks, and a phase change material. The results indicate that with low temperature heat storage, domestic load shifting is feasible over a few days. Beyond this timescale, the very large storage volumes required make integration in dwellings problematic. Supporting load shifting over 1–2 weeks is feasible with high temperature storage. Retention of heat over periods longer than this is challenging, even with significant levels of insulation. Seasonal storage of heat in an encapsulated store appeared impractical in all cases modelled due to the volume of material required

Widespread seasonal gene expression reveals annual differences in human immunity and physiology.

Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease.The Gambian study providing data for analysis was supported by core funding MC-A760-5QX00 to the International Nutrition Group by the UK Medical Research Council (MRC) and the UK Department for the International Development (DFID) under the MRC/DFID Concordat agreement. This work was supported by the JDRF UK Centre for Diabetes-Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003), the JDRF (9-2011-253), the Wellcome Trust (WT061858/091157), the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC) and the Medical Research Council (MRC) Cusrow Wadia Fund. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007–2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (WT100140). X.C.D. was a University of Cambridge/Wellcome Trust Infection and Immunity PhD student. R.C.F. is funded by a JDRF post-doctoral fellowship (3-2011-374). C.W. and H.G are funded by the Wellcome Trust (WT089989). The BABYDIET study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG ZI-310/14-1 to-4), the JDRF (JDRF 17-2012-16 and 1-2006-665) and the German Center for Diabetes Research (DZD e.V.). E.B. is supported by the DFG Research Center and Cluster of Excellence—Center for Regenerative Therapies Dresden (FZ 111).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150512/ncomms8000/full/ncomms8000.html

A Comparative Analysis of OpenET for Evaluating Evapotranspiration in California Almond Orchards

The almond industry in California faces water management challenges that are being exacerbated by droughts, climate change, and groundwater sustainability legislation. The Tree-crop Remote sensing of Evapotranspiration eXperiment (T-REX) aims to explore opportunities to improve precision irrigation management for woody perennial cropping systems. Almond orchards in the California Central Valley were equipped with eddy covariance flux measurements to evaluate satellite remote sensing-based evapotranspiration (RSET) models. OpenET provides high-resolution (30-m spatial and daily temporal) RSET data, synthesizing decades of research for practical water management. This study provides an evaluation of OpenET performance at six almond sites covering a large range in soils, age, and variety. It also compares OpenET ensemble evapotranspiration (ET) data with applied irrigation and precipitation records over an additional 148 almond orchards located in the Central Valley of California. Results show OpenET models, including the ensemble ET value, produced reasonable and actionable ET values, with overall coefficient of determination (R2) and mean absolute error values of 0.73- and 0.95-mm d−1 at the daily time step, respectively. However, given the temporal sampling of Landsat (8-day revisit) and the interpolation methods used, the assessed ET models had difficulty in capturing short-term variability in almond ET; for example, the rapid decline in measured ET observed as a response to lack of irrigation preceding and during almond harvest. The study also drew attention to the spatial complexity in scenarios where irrigated orchards are surrounded by hot/dry areas, causing discrepancies between measured and modeled ET values. In comparison with irrigation records, OpenET ensemble ET was capable of quantifying water input (applied irrigation + precipitation) in almond orchards to within 13 % when evaluating monthly data. Initial results presented here reinforce the idea that RSET models, such as in OpenET, are powerful tools, yet their application requires nuanced understanding and careful consideration of local conditions

Isolation and fine mapping of Rps6: An intermediate host resistance gene in barley to wheat stripe rust

A plant may be considered a nonhost of a pathogen if all known genotypes of a plant species are resistant to all known isolates of a pathogen species. However, if a small number of genotypes are susceptible to some known isolates of a pathogen species this plant maybe considered an intermediate host. Barley (Hordeum vulgare) is an intermediate host for Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust. We wanted to understand the genetic architecture underlying resistance to Pst and to determine whether any overlap exists with resistance to the host pathogen, Puccinia striiformis f. sp. hordei (Psh). We mapped Pst resistance to chromosome 7H and show that host and intermediate host resistance is genetically uncoupled. Therefore, we designate this resistance locus Rps6. We used phenotypic and genotypic selection on F2:3 families to isolate Rps6 and fine mapped the locus to a 0.1 cM region. Anchoring of the Rps6 locus to the barley physical map placed the region on two adjacent fingerprinted contigs. Efforts are now underway to sequence the minimal tiling path and to delimit the physical region harbouring Rps6. This will facilitate additional marker development and permit identification of candidate genes in the region

The QUaD Galactic Plane Survey. I. Maps and Analysis of Diffuse Emission

We present a survey of ~800 deg$^{2}$ of the galactic plane observed with the QUaD telescope. The primary products of the survey are maps of Stokes I, Q, and U parameters at 100 and 150 GHz, with spatial resolution of 5' and 3'.5, respectively. Two regions are covered, spanning approximately 245°-295° and 315°-5° in the galactic longitude l and –4° < b < +4° in the galactic latitude b. At 0°.02 square pixel size, the median sensitivity is 74 and 107 kJy sr$^{–1}$ at 100 GHz and 150 GHz respectively in I, and 98 and 120 kJy sr$^{–1}$ for Q and U. In total intensity, we find an average spectral index of α = 2.35 ± 0.01(stat) ± 0.02(sys) for |b| ≤ 1°, indicative of emission components other than thermal dust. A comparison to published dust, synchrotron, and free-free models implies an excess of emission in the 100 GHz QUaD band, while better agreement is found at 150 GHz. A smaller excess is observed when comparing QUaD 100 GHz data to the WMAP five-year W band; in this case, the excess is likely due to the wider bandwidth of QUaD. Combining the QUaD and WMAP data, a two-component spectral fit to the inner galactic plane (|b| ≤ 1°) yields mean spectral indices of α s = –0.32 ± 0.03 and α$_{d}$ = 2.84 ± 0.03; the former is interpreted as a combination of the spectral indices of synchrotron, free-free, and dust, while the second is largely attributed to the thermal dust continuum. In the same galactic latitude range, the polarization data show a high degree of alignment perpendicular to the expected galactic magnetic field direction, and exhibit mean polarization fraction 1.38 ± 0.08(stat) ± 0.1(sys)% at 100 GHz and 1.70 ± 0.06(stat) ± 0.1(sys)% at 150 GHz. We find agreement in polarization fraction between QUaD 100 GHz and the WMAP W band, the latter giving 1.1% ± 0.4%.Astronom

Cryogenic testing of the integrated Ariel space telescope: design of the optical test equipment

In this proceeding, we present the development of the Optical Ground Support Equipment (OGSE) used for payload-level testing of the Ariel space mission. Ariel is an ESA mission that will use the transit spectroscopy method to observe the atmospheres of nominally ~1000 exoplanets. Ariel is a 1 m class cryogenic (∼ 40 K) space telescope that will be placed in a halo orbit around the Earth-Sun L2 point. To detect atmospheric molecular absorption features, Ariel will produce medium-resolution spectra (R ≥ 15) using three spectroscopic channels covering 1.1 – 7.9 μm as well as having photometric channels covering 0.5 – 1.1 μm. To achieve Ariel’s science goals, the payload requires detailed calibration and performance verification. The payload-level performance verification of the Ariel payload will take place in 2026 in a 5-meter vacuum chamber at the Rutherford Appleton Laboratory’s Space Instruments Test Facility. The payload will be enclosed in a Cryogenic Test Rig (CTR) to provide a space-like (~35 K) thermal environment and is illuminated by the OGSE. The OGSE provides point as well as extended source illumination across Ariel’s full wavelength range. The OGSE design also includes a series of mechanisms and features to enable the various illumination conditions required to test Ariel. Here we report design updates to the OGSE after a preliminary design review (PDR). Since PDR, there have been substantial revisions to the OGSE architecture. In this proceeding, we describe the evolution of the OGSE architecture. The updated OGSE design will then be presented