Long-term variations in abundance and distribution of sulfuric acid vapor in the Venus atmosphere inferred from Pioneer Venus and Magellan radio occultation studies

Radio occultation experiments have been used to study various properties of planetary atmospheres, including pressure and temperature profiles, and the abundance profiles of absorbing constituents in those planetary atmospheres. However, the reduction of amplitude data from such experiments to determine abundance profiles requires the application of the inverse Abel transform (IAT) and numerical differentiation of experimental data. These two operations preferentially amplify measurement errors above the true signal underlying the data. A new technique for processing radio occultation data has been developed that greatly reduces the errors in the derived absorptivity and abundance profiles. This technique has been applied to datasets acquired from Pioneer Venus Orbiter radio occultation studies and more recently to experiments conducted with the Magellan spacecraft. While primarily designed for radar studies of the Venus surface, the high radiated power (EIRP) from the Magellan spacecraft makes it an ideal transmitter for measuring the refractivity and absorptivity of the Venus atmosphere by such experiments. The longevity of the Pioneer Venus Orbiter has made it possible to study long-term changes in the abundance and distribution of sulfuric acid vapor, H2SO4(g), in the Venus atmosphere between 1979 and 1992. The abundance of H2SO4(g) can be inferred from vertical profiles of 13-cm absorptivity profiles retrieved from radio occultation experiments. Data from 1979 and 1986-87 suggest that the abundance of H2SO4(g) at latitudes northward of 70 deg decreased over this time period. This change may be due to a period of active volcanism in the late 1970s followed by a relative quiescent period, or some other dynamic process in the Venus atmosphere. While the cause is not certain, such changes must be incorporated into dynamic models of the Venus atmosphere. Potentially, the Magellan spacecraft will extend the results of Pioneer Venus Orbiter and allow the continued monitoring of the abundance of distribution of H2SO4(g) in the Venus atmosphere, as well as other interesting atmospheric properties. Without such measurements it will be difficult to address other issues such as the short-term spatial variability of the abundance of H2SO4(g) at similar latitudes in Venus atmosphere, and the identities of particles responsible for large-scale variations observed in NIR images

\u3cem\u3eArabidopsis\u3c/em\u3e AZI1 Family Proteins Mediate Signal Mobilization for Systemic Defence Priming

Priming is a major mechanism behind the immunological \u27memory\u27 observed during two key plant systemic defences: systemic acquired resistance (SAR) and induced systemic resistance (ISR). Lipid-derived azelaic acid (AZA) is a mobile priming signal. Here, we show that the lipid transfer protein (LTP)-like AZI1 and its closest paralog EARLI1 are necessary for SAR, ISR and the systemic movement and uptake of AZA in Arabidopsis. Imaging and fractionation studies indicate that AZI1 and EARLI1 localize to expected places for lipid exchange/movement to occur. These are the ER/plasmodesmata, chloroplast outer envelopes and membrane contact sites between them. Furthermore, these LTP-like proteins form complexes and act at the site of SAR establishment. The plastid targeting of AZI1 and AZI1 paralogs occurs through a mechanism that may enable/facilitate their roles in signal mobilization

Seniority and Job Stability: A Quantile Regression Approach Using Matched Employer-Employee Data

Job mobility and employment durations can be explained by different theoretical approaches, such as job matching or human capital theory or dual labor market approaches. These models may, however, apply to different degrees at different durations in the employment spell. Standard empirical techniques, such as hazard rate analysis, cannot deal with this problem. In this paper, we apply censored quantile regression techniques to estimate employment durations of male workers in Germany. Our results give some support to the job matching model: individuals with a high risk of being bad matches exhibit higher exit rates initially, but the effect fades out over time. By contrast, the influence of human capital variables such as education and further training decreases with employment duration, which is inconsistent with the notion of increasing match-specific rents due to human capital accumulation. The results also suggest that the effects of certain labor market institutions, such as works councils, differ markedly between short-term and long-term employment, supporting the view that institutions give rise to dual labor markets

Implications of the Ammonia Distribution on Jupiter from 1 to 100 Bars as Measured by the Juno Microwave Radiometer

The latitude-altitude map of ammonia mixing ratio shows an ammonia-rich zone at 0-5degN, with mixing ratios of 320-340 ppm, extending from 40-60 bars up to the ammonia cloud base at 0.7 bars. Ammonia-poor air occupies a belt from 5-20degN. We argue that downdrafts as well as updrafts are needed in the 0-5degN zone to balance the upward ammonia flux. Outside the 0-20degN region, the belt-zone signature is weaker. At latitudes out to +/-40deg, there is an ammonia-rich layer from cloud base down to 2 bars which we argue is caused by falling precipitation. Below, there is an ammonia-poor layer with a minimum at 6 bars. Unanswered questions include how the ammonia-poor layer is maintained, why the belt-zone structure is barely evident in the ammonia distribution outside 0-20degN, and how the internal heat is transported through the ammonia-poor layer to the ammonia cloud base

Joint effects of known type 2 diabetes susceptibility loci in genome-wide association study of Singapore Chinese: The Singapore Chinese health study

Background: Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study. Methods: 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r2>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ±100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis. Results: Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69-2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72×10-14). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs. Conclusions: While diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease. © 2014 Chen et al

Useful pharmacodynamic endpoints in children: selection, measurement, and next steps.

Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families.Pediatric Research advance online publication, 11 April 2018; doi:10.1038/pr.2018.38

Paclitaxel-Loaded Cationic Fluid Lipid Nanodiscs and Liposomes with Brush-Conformation PEG Chains Penetrate Breast Tumors and Trigger Caspase‑3 Activation

Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLsPTX) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLsPTX and PTX-containing fluid lipid nanodiscs (nanodiscsPTX). These CLsPTX and nanodiscsPTX show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, in vivo circulation half-life, and biodistribution of systemically administered CLsPTX and nanodiscsPTX and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on fluid rather than solid lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLsPTX and nanodiscsPTX was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy