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

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range

Modeling NH4NO3 over the San Joaquin Valley During the 2013 DISCOVER-AQ Campaign

The San Joaquin Valley (SJV) of California experiences high concentrations of PM2.5 (particulate matter with aerodynamic diameter 2.5 m) during episodes of meteorological stagnation in winter. Modeling PM2.5 NH4NO3 during these episodes is challenging because it involves simulating meteorology in complex terrain under low wind speed and vertically stratified conditions, representing complex pollutant emissions distributions, and simulating daytime and nighttime chemistry that can be influenced by the mixing of urban and rural air masses. A rich dataset of observations related to NH4NO3 formation was acquired during multiple periods of elevated NH4NO3 during the DISCOVER-AQ (Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality) field campaign in SJV in January and February 2013. Here, NH4NO3 is simulated during the SJV DISCOVER-AQ study period with the Community Multiscale Air Quality (CMAQ) model version 5.1, predictions are evaluated with the DISCOVER-AQ dataset, and process analysis modeling is used to quantify HNO3 production rates. Simulated NO3- generally agrees well with routine monitoring of 24-h average NO3-, but comparisons with hourly average NO3- measurements in Fresno revealed differences at higher time resolution. Predictions of gas-particle partitioning of total nitrate (HNO3 + NO3-) and NHx (NH3 + NH4+) generally agreed well with measurements in Fresno, although partitioning of total nitrate to HNO3 was sometimes overestimated at low relative humidity in afternoon. Gas-particle partitioning results indicate that NH4NO3 formation is limited by HNO3 availability in both the model and ambient. NH3 mixing ratios are underestimated, particularly in areas with large agricultural activity, and the spatial allocation of NH3 emissions could benefit from additional work, especially near Hanford. HNO3 production via daytime and nighttime pathways is reasonably consistent with the conceptual model of NH4NO3 formation in SJV, and production peaked aloft between about 160 and 240 m in the model. During a period of elevated NH4NO3, the model predicted that the OH + NO2 pathway contributed 46% to total HNO3 production in SJV and the N2O5 heterogeneous hydrolysis pathway contributed 54%. The relative importance of the OH + NO2 pathway for HNO3 production is predicted to increase as NOx emissions decrease

mRNA Display Selection of an Optimized MDM2-Binding Peptide That Potently Inhibits MDM2-p53 Interaction

p53 is a tumor suppressor protein that prevents tumorigenesis through cell cycle arrest or apoptosis of cells in response to cellular stress such as DNA damage. Because the oncoprotein MDM2 interacts with p53 and inhibits its activity, MDM2-p53 interaction has been a major target for the development of anticancer drugs. While previous studies have used phage display to identify peptides (such as DI) that inhibit the MDM2-p53 interaction, these peptides were not sufficiently optimized because the size of the phage-displayed random peptide libraries did not cover all of the possible sequences. In this study, we performed selection of MDM2-binding peptides from large random peptide libraries in two stages using mRNA display. We identified an optimal peptide named MIP that inhibited the MDM2-p53 and MDMX-p53 interactions 29- and 13-fold more effectively than DI, respectively. Expression of MIP fused to the thioredoxin scaffold protein in living cells by adenovirus caused stabilization of p53 through its interaction with MDM2, resulting in activation of the p53 pathway. Furthermore, expression of MIP also inhibited tumor cell proliferation in a p53-dependent manner more potently than DI. These results show that two-stage, mRNA-displayed peptide selection is useful for the rapid identification of potent peptides that target oncoproteins

Observed Kinetic Parameters during the Torrefaction of Red Oak (Quercus rubra) in a Pilot Rotary Kiln Reactor

The torrefaction of red oak (Quercus rubra) was performed in a pilot rotary kiln reactor, and the apparent kinetic results were compared with the results of torrefaction performed in a bench-scale fluidized reactor. Mass loss, gross calorific analyses, ultimate analyses, and proximate analyses were applied to the final torrefied material. The experimental torrefaction temperatures were 250, 275, 300, and 325 °C, and the experimental total torrefaction times were 20, 35, 50, and 80 min. A significant variation of the energy content occurred in the range of temperature between 275 and 300 °C, with the energy yield changing from 97.5% to 83.6%, respectively. The molar ratios H:C:O for the torrefied red oak presented a behavior independent of the experimental equipment when the temperature ranged between 250 and 325 °C. For the torrefaction process of red oak in the pilot rotary kiln reactor, a first-order reaction and one-step kinetic model were fitted with a maximum error of about 7.5% at 325 °C. The observed reaction rate constant (k) for the rotary reactor was 0.072 min−1 at 300 °C, which was 71% lower than the reaction rate constant for torrefied red oak in a bench-scale fluidized reactor. Arrhenius analysis determined an activation energy of 20.4 kJ/mol and a frequency factor of 5.22 min−1. The results suggest significant external heat and mass-transfer resistances in the rotary system

A flexible and robust neural network IASI-NH₃ retrieval algorithm

International audienceIn this paper, we describe a new flexible and robust NH3 retrieval algorithm from measurements of the Infrared Atmospheric Sounding Interferometer (IASI). The method is based on the calculation of a spectral hyperspectral range index (HRI) and subsequent conversion to NH3 columns via a neural network. It is an extension of the method presented in Van Damme et al. (2014a) who used lookup tables (LUT) for the radiance-concentration conversion. The new method inherits the advantages of the LUT-based method while providing several significant improvements. These include the following: (1) Complete temperature and humidity vertical profiles can be accounted for. (2) Third-party NH3 vertical profile information can be used. (3) Reported positive biases of LUT retrieval are reduced, and finally (4) a full measurement uncertainty characterization is provided. A running theme in this study, related to item (2), is the importance of the assumed vertical NH3 profile. We demonstrate the advantages of allowing variable profile shapes in the retrieval. As an example, we analyze how the retrievals change when all NH3 is assumed to be confined to the boundary layer. We analyze different averaging procedures in use for NH3 in the literature, introduced to cope with the variable measurement sensitivity and derive global averaged distributions for the year 2013. A comparison with a GEOS-Chem modeled global distribution is also presented, showing a general good correspondence (within ±3 × 1015 molecules.cm−2) over most of the Northern Hemisphere. However, IASI finds mean columns about 1–1.5 × 1016 molecules.cm−2 (∼50–60%) lower than GEOS-Chem for India and the North China plain

Local maternal control of seed size by KLUH/CYP78A5-dependent growth signaling

Seed development in plants involves the coordinated growth of the embryo, endosperm, and maternal tissue. Several genes have been identified that influence seed size by acting maternally, such as AUXIN RESPONSE FACTOR2, APETALA2, and DA1. However, given the lack of gain-of-function effects of these genes on seed size, it is unclear whether their activity levels are limiting in WT plants and whether they could thus be used to regulate seed size in development or evolution. Also, whether the altered seed sizes reflect local gene activity or global physiological changes is unknown. Here, we demonstrate that the cytochrome P450 KLUH (KLU) regulates seed size. KLU acts locally in developing flowers to promote seed growth, and its activity level is limiting for seed growth in WT. KLU is expressed in the inner integument of developing ovules, where it non-cell autonomously stimulates cell proliferation, thus determining the growth potential of the seed coat and seed. A KLU-induced increase in seed size leads to larger seedlings and higher relative oil content of the seeds. Genetic analyses indicate that KLU acts independently of other tested maternal factors that influence integument cell proliferation. Thus, the level of KLU-dependent growth factor signaling determines size in ovules and seeds, suggesting this pathway as a target for crop improvement