Three-Dimensional Discrete Element Simulations of Direct Shear Tests

Using discrete element simulations, one can monitor the micro-mechanisms driving the macroresponse of granular materials and quantify the evolution of local stress and strain values. However, it is important to couple the se simulations with carefully controlled physical tests for validation and insight. Only then can findings about the micro- mechanics of the material response be made with confidence. Moreover, the sensitivity of the observed response to the test boundary conditions can be analyzed in some detail. The results of three-dimensional discrete element simulations of direct shear tests and as well as complementary physical tests on specimens of steel balls are presented in this paper. Previous discrete element analyses of the direct shear test have been restricted to two-dimensional simulations. For the simulations presented here, an analysis of the internal stresses and contact forces illustrates the three-dimensional nature of the material response. The distribution of contact forces in the specimen at larger strain values, however, was found to be qualitatively similar to the two-dimensional results of Zhang and Thornton (2002). Similarities were also observed between the distrib ution of local strain values and the distribution of strains obtained by Potts et al (1987) in a finite element analysis of the direct shear test. The simulation results indicated that the material response is the stress dependent. However, the response observed in the simulations was found to be significantly stiffer than that observed in the physical tests. The angle of internal friction for the simulations was also about 3o lower than that measured in the laboratory tests. Further laboratory tests and simulations are required to establish the source of the observed discrepancies

Heterogeneous Ice Nucleation by Soufriere Hills Volcanic Ash Immersed in Water Droplets

Fine particles of ash emitted during volcanic eruptions may sporadically influence cloud properties on a regional or global scale as well as influencing the dynamics of volcanic clouds and the subsequent dispersion of volcanic aerosol and gases. It has been shown that volcanic ash can trigger ice nucleation, but ash from relatively few volcanoes has been studied for its ice nucleating ability. In this study we quantify the efficiency with which ash from the Soufriere Hills volcano on Montserrat nucleates ice when immersed in supercooled water droplets. Using an ash sample from the 11th February 2010 eruption, we report ice nucleating efficiencies from 246 to 265 K. This wide range of temperatures was achieved using two separate droplet freezing instruments, one employing nanolitre droplets, the other using microlitre droplets. Soufriere Hills volcanic ash was significantly more efficient than all other ash samples that have been previously examined. At present the reasons for these differences are not understood, but may be related to mineralogy, amorphous content and surface chemistry

Ice nucleation by fertile soil dusts: Relative importance of mineral and biogenic components

Agricultural dust emissions have been estimated to contribute around 20% to the global dust burden. In contrast to dusts from arid source regions, the ice-nucleating abilities of which have been relatively well studied, soil dusts from fertile sources often contain a substantial fraction of organic matter. Using an experimental methodology which is sensitive to a wide range of ice nucleation efficiencies, we have characterised the immersion mode ice-nucleating activities of dusts (d<11 μ m) extracted from fertile soils collected at four locations around England. By controlling droplet sizes, which ranged in volume from 10 to 10 L (concentration=0.02 to 0.1 wt% dust), we have been able to determine the ice nucleation behaviour of soil dust particles at temperatures ranging from 267K (-6°C) down to the homogeneous limit of freezing at about 237K (-36°C). At temperatures above 258K (-15°C) we find that the ice-nucleating activity of soil dusts is diminished by heat treatment or digestion with hydrogen peroxide, suggesting that a major fraction of the ice nuclei stems from biogenic components in the soil. However, below 258 K, we find that the ice active site densities tend towards those expected from the mineral components in the soils, suggesting that the inorganic fraction of soil dusts, in particular the K-feldspar fraction, becomes increasingly important in the initiation of the ice phase at lower temperatures. We conclude that dusts from agricultural activities could contribute significantly to atmospheric IN concentrations, if such dusts exhibit similar activities to those observed in the current laboratory study

Upper tropospheric ozone production from lightning NOx-impacted convection: Smoke ingestion case study from the DC3 campaign

©2015. American Geophysical Union. All Rights Reserved. As part of the Deep Convective Cloud and Chemistry (DC3) experiment, the National Science Foundation/National Center for Atmospheric Research (NCAR) Gulfstream-V (GV) and NASA DC-8 research aircraft probed the chemical composition of the inflow and outflow of two convective storms (north storm, NS, south storm, SS) originating in the Colorado region on 22 June 2012, a time when the High Park wildfire was active in the area. A wide range of trace species were measured on board both aircraft including biomass burning (BB) tracers hydrogen cyanide (HCN) and acetonitrile (ACN). Acrolein, a much shorter lived tracer for BB, was also quantified on the GV. The data demonstrated that the NS had ingested fresh smoke from the High Park fire and as a consequence had a higher VOC OH reactivity than the SS. The SS lofted aged fire tracers along with other boundary layer ozone precursors and was more impacted by lightning NOx (LNOx) than the NS. The NCAR master mechanism box model was initialized with measurements made in the outflow of the two storms. The NS and SS were predicted to produce 11 and 14ppbv of O3, respectively, downwind of the storm over 2days. Sensitivity tests revealed that the ozone production potential of the SS was highly dependent on LNOx. Normalized excess mixing ratios, ΔX/ΔCO, for HCN and ACN were determined in both the fire plume and the storm outflow and found to be 7.0±0.5 and 2.3±0.5pptvppbv-1, respectively, and 1.4±0.3pptvppbv-1 for acrolein in the outflow only

Improvement in accuracy of multiple sequence alignment using novel group-to-group sequence alignment algorithm with piecewise linear gap cost

BACKGROUND: Multiple sequence alignment (MSA) is a useful tool in bioinformatics. Although many MSA algorithms have been developed, there is still room for improvement in accuracy and speed. In the alignment of a family of protein sequences, global MSA algorithms perform better than local ones in many cases, while local ones perform better than global ones when some sequences have long insertions or deletions (indels) relative to others. Many recent leading MSA algorithms have incorporated pairwise alignment information obtained from a mixture of sources into their scoring system to improve accuracy of alignment containing long indels. RESULTS: We propose a novel group-to-group sequence alignment algorithm that uses a piecewise linear gap cost. We developed a program called PRIME, which employs our proposed algorithm to optimize the well-defined sum-of-pairs score. PRIME stands for Profile-based Randomized Iteration MEthod. We evaluated PRIME and some recent MSA programs using BAliBASE version 3.0 and PREFAB version 4.0 benchmarks. The results of benchmark tests showed that PRIME can construct accurate alignments comparable to the most accurate programs currently available, including L-INS-i of MAFFT, ProbCons, and T-Coffee. CONCLUSION: PRIME enables users to construct accurate alignments without having to employ pairwise alignment information. PRIME is available at

Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma

<p>Abstract</p> <p>Background</p> <p>Asthma can be difficult to diagnose, but bronchial provocation with methacholine, exercise or mannitol is helpful when used to identify bronchial hyperresponsiveness (BHR), a key feature of the disease. The utility of these tests in subjects with signs and symptoms of asthma but without a clear diagnosis has not been investigated. We investigated the sensitivity and specificity of mannitol to identify exercise-induced bronchoconstriction (EIB) as a manifestation of BHR; compared this with methacholine; and compared the sensitivity and specificity of mannitol and methacholine for a clinician diagnosis of asthma.</p> <p>Methods</p> <p>509 people (6–50 yr) were enrolled, 78% were atopic, median FEV₁92.5% predicted, and a low NAEPPII asthma score of 1.2. Subjects with symptoms of seasonal allergy were excluded. BHR to exercise was defined as a ≥ 10% fall in FEV₁on at least one of two tests, to methacholine a PC₂₀≤ 16 mg/ml and to mannitol a 15% fall in FEV₁at ≤ 635 mg or a 10% fall between doses. The clinician diagnosis of asthma was made on examination, history, skin tests, questionnaire and response to exercise but they were blind to the mannitol and methacholine results.</p> <p>Results</p> <p>Mannitol and methacholine were therapeutically equivalent to identify EIB, a clinician diagnosis of asthma, and prevalence of BHR. The sensitivity/specificity of mannitol to identify EIB was 59%/65% and for methacholine it was 56%/69%. The BHR was mild. Mean EIB % fall in FEV₁in subjects positive to exercise was 19%, (SD 9.2), mannitol PD₁₅158 (CI:129,193) mg, and methacholine PC₂₀2.1(CI:1.7, 2.6)mg/ml. The prevalence of BHR was the same: for exercise (43.5%), mannitol (44.8%), and methacholine (41.6%) with a test agreement between 62 & 69%. The sensitivity and specificity for a clinician diagnosis of asthma was 56%/73% for mannitol and 51%/75% for methacholine. The sensitivity increased to 73% and 72% for mannitol and methacholine when two exercise tests were positive.</p> <p>Conclusion</p> <p>In this group with normal FEV₁, mild symptoms, and mild BHR, the sensitivity and specificity for both mannitol and methacholine to identify EIB and a clinician diagnosis of asthma were equivalent, but lower than previously documented in well-defined populations.</p> <p>Trial registration</p> <p>This was a multi-center trial comprising 25 sites across the United States of America. (NCT0025229).</p

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni.

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics