The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements

Evaluation of single and multiple Doppler lidar techniques to measure complex flow during the XPIA field campaign

Accurate three-dimensional information of wind flow fields can be an important tool in not only visualizing complex flow but also understanding the underlying physical processes and improving flow modeling. However, a thorough analysis of the measurement uncertainties is required to properly interpret results. The XPIA (eXperimental Planetary boundary layer Instrumentation Assessment) field campaign conducted at the Boulder Atmospheric Observatory (BAO) in Erie, CO, from 2 March to 31 May 2015 brought together a large suite of in situ and remote sensing measurement platforms to evaluate complex flow measurement strategies. In this paper, measurement uncertainties for different single and multi-Doppler strategies using simple scan geometries (conical, vertical plane and staring) are investigated. The tradeoffs (such as time–space resolution vs. spatial coverage) among the different measurement techniques are evaluated using co-located measurements made near the BAO tower. Sensitivity of the single-/multi-Doppler measurement uncertainties to averaging period are investigated using the sonic anemometers installed on the BAO tower as the standard reference. Finally, the radiometer measurements are used to partition the measurement periods as a function of atmospheric stability to determine their effect on measurement uncertainty. It was found that with an increase in spatial coverage and measurement complexity, the uncertainty in the wind measurement also increased. For multi-Doppler techniques, the increase in uncertainty for temporally uncoordinated measurements is possibly due to requiring additional assumptions of stationarity along with horizontal homogeneity and less representative line-of-sight velocity statistics. It was also found that wind speed measurement uncertainty was lower during stable conditions compared to unstable conditions

The immersion mode ice nucleation behavior of mineral dusts: A comparison of different pure and surface modified dusts

In this study we present results from immersion freezing experiments with size-segregated mineral dust particles. Besides two already existing data sets for Arizona Test Dust (ATD), and Fluka kaolinite, we show two new data sets for illite-NX, which consists mainly of illite, a clay mineral, and feldspar, a common crustal material. The experiments were carried out with the Leipzig Aerosol Cloud Interaction Simulator. After comparing the different dust samples, it became obvious that the freezing ability was positively correlated with the K-feldspar content. Furthermore, a comparison of the composition of the ATD, illite-NX, and feldspar samples suggests that within the K-feldspars, microcline is more ice nucleation active than orthoclase. A coating with sulfuric acid leads to a decrease in the ice nucleation ability of all mineral dusts, with the effect being more pronounced for the feldspar sample. Key Points The freezing ability of mineral dusts correlated with the K-feldspar contentAmong feldspars, microcline shows a better ice nucleation ability than orthoclaseAfter coating, all investigated dusts feature a similar ice nucleation abilit

Overview of the 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES)

Substantial uncertainties still exist in the scientific understanding of the possible interactions between urban and natural (biogenic) emissions in the production and transformation of atmospheric aerosol and the resulting impact on climate change. The US Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) program's Carbonaceous Aerosol and Radiative Effects Study (CARES) carried out in June 2010 in Central Valley, California, was a comprehensive effort designed to improve this understanding. The primary objective of the field study was to investigate the evolution of secondary organic and black carbon aerosols and their climate-related properties in the Sacramento urban plume as it was routinely transported into the forested Sierra Nevada foothills area. Urban aerosols and trace gases experienced significant physical and chemical transformations as they mixed with the reactive biogenic hydrocarbons emitted from the forest. Two heavily-instrumented ground sites – one within the Sacramento urban area and another about 40 km to the northeast in the foothills area – were set up to characterize the evolution of meteorological variables, trace gases, aerosol precursors, aerosol size, composition, and climate-related properties in freshly polluted and "aged" urban air. On selected days, the DOE G-1 aircraft was deployed to make similar measurements upwind and across the evolving Sacramento plume in the morning and again in the afternoon. The NASA B-200 aircraft, carrying remote sensing instruments, was also deployed to characterize the vertical and horizontal distribution of aerosols and aerosol optical properties within and around the plume. This overview provides: (a) the scientific background and motivation for the study, (b) the operational and logistical information pertinent to the execution of the study, (c) an overview of key observations and initial findings from the aircraft and ground-based sampling platforms, and (d) a roadmap of planned data analyses and focused modeling efforts that will facilitate the integration of new knowledge into improved representations of key aerosol processes and properties in climate models.United States. Dept. of Energy. Atmospheric System Research Program (Contract DE-AC06-76RLO 1830)United States. National Oceanic and Atmospheric AdministrationUnited States. National Aeronautics and Space Administration. HQ Science Mission Directorate Radiation Sciences ProgramUnited States. National Aeronautics and Space Administration. CALIPSO ProgramUnited States. Dept. of Energy. Atmospheric Radiation Measurement Program (Interagency Agreement No. DE-AI02-05ER63985

Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

<p>Abstract</p> <p>Background</p> <p>DNA methylation in the <it>SHOX2 </it>locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with <it>SHOX2 </it>gene expression and/or copy number alterations. An amplification of the <it>SHOX2 </it>gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.</p> <p>Methods</p> <p><it>SHOX2 </it>expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect <it>SHOX2 </it>DNA methylation levels. <it>SHOX2 </it>expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.</p> <p>Results</p> <p>A hypermethylation of the <it>SHOX2 </it>locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the <it>SHOX2 </it>gene showed no difference.</p> <p>Conclusions</p> <p>Frequent gene amplification correlated with hypermethylation of the <it>SHOX2 </it>gene locus. This concerted effect qualifies <it>SHOX2 </it>DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.</p

SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates

<p>Abstract</p> <p>Background</p> <p>This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.</p> <p>Methods</p> <p>Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.</p> <p>Results</p> <p>Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).</p> <p>Conclusions</p> <p>Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.</p

Tropical intraseasonal variability in 14 IPCC AR4 climate models. Part I: Convective signals

This study evaluates the tropical intraseasonal variability, especially the fidelity of The results show that current state-of-the-art GCMs still have significant problems and display a wide range of skill in simulating the tropical intraseasonal variability. The total intraseasonal (2-128 day) variance of precipitation is too weak in most of the models. About half of the models have signals of convectively coupled equatorial waves, with Kelvin and MRG-EIG waves especially prominent. However, the variances are generally too weak for all wave modes except the EIG wave, and the phase speeds are generally too fast, being scaled to excessively deep equivalent depths. An interesting result is that this scaling is consistent within a given model across modes, in that both the symmetric and antisymmetric modes scale similarly to a certain equivalent depth. Excessively deep equivalent depths suggest that these models may not have a large enough reduction in their &quot;effective static stability&quot; due to diabatic heating. 3 The MJO variance approaches the observed value in only two of the 14 models, but is less than half of the observed value in the other 12 models. The ratio between the eastward MJO variance and the variance of its westward counterpart is too small in most of the models, which is consistent with the lack of highly coherent eastward propagation of the MJO in many models. Moreover, the MJO variance in 13 of the 14 models does not come from a pronounced spectral peak, but usually is associated with an overreddened spectrum, which in turn is associated with a too strong persistence of equatorial precipitation. The two models that arguably do best at simulating the MJO are the only ones having convective closures/triggers linked in some way to moisture convergence

A conceptual framework for time and space scale interactions in the climate system

Interactions involving various space and time scales, both within the tropics and between the tropics and midlatitudes, are ubiquitous in the climate system. The concept of longer time scales and larger space scales setting the base state for processes on shorter time scales and smaller space scales is explored. Decadal time scale base states of the coupled climate system set the context for the manifestation of interannual time scales (El Nino/Southern Oscillation, ENSO and tropospheric biennial oscillation, TBO) which are influenced by and interact with the annual cycle and seasonal time scales. Those base states in turn influence the large-scale coupled processes involved with intraseasonal and submonthly time scales, tied to tropical-tropical and tropical-midlatitude teleconnections. All of these set the base state for processes on the synoptic and mesoscale and regional/local space scales. Events at those relatively short time scales and small space scales may then affect the longer time scale and larger space scale processes in turn, reaching back out to submonthly, intraseasonal, seasonal, annual, TBO, ENSO and decadal. Global coupled models can capture some elements of the decadal, ENSO, TBO, annual and seasonal time scales with the associated global space scales. However, coupled models are less successful at simulating phenomena at subseasonal and shorter time scales with hemispheric and smaller space scales. Due to the synergistic interactions of the time and space scales, a high priority must be placed on improved simulations of all the time and space scales in the climate system (particularly the subseasonal time scales and hemispheric and smaller space scales which are not well simulated at present) if we hope to successfully forecast phenomena beyond the synoptic scales

Lidar Uncertainty Measurement Experiment (LUMEX) – Understanding Sampling Errors

Coherent Doppler LIDAR (Light Detection and Ranging) has been widely used to provide measurements of several boundary layer parameters such as profiles of wind speed, wind direction, vertical velocity statistics, mixing layer heights and turbulent kinetic energy (TKE). An important aspect of providing this wide range of meteorological data is to properly characterize the uncertainty associated with these measurements. With the above intent in mind, the Lidar Uncertainty Measurement Experiment (LUMEX) was conducted at Erie, Colorado during the period June 23rd to July 13th, 2014. The major goals of this experiment were the following: Characterize sampling error for vertical velocity statistic

Entrainment of stratospheric air and Asian pollution by the convective boundary layer in the southwestern U.S.

International audienceA series of deep stratospheric intrusions in late May 2013 increased the daily maximum 8 h surface ozone (O 3) concentrations to more than 70 parts per billion by volume (ppbv) at rural and urban surface monitors in California and Nevada. This influx of ozone-rich lower stratospheric air and entrained Asian pollution persisted for more than 5 days and contributed to exceedances of the 2008 8 h national ambient air quality standard of 75 ppbv on 21 and 25 May in Clark County, NV. Exceedances would also have occurred on 22 and 23 May had the new standard of 70 ppbv been in effect. In this paper, we examine this episode using lidar measurements from a high-elevation site on Angel Peak, NV, and surface measurements from NOAA, the Clark County, Nevada Department of Air Quality, the Environmental Protection Agency Air Quality System, and the Nevada Rural Ozone Initiative. These measurements, together with analyses from the National Centers for Environmental Prediction/North American Regional Reanalysis