564 research outputs found
Atmospheric cycles of nitrogen oxides and ammonia
The atmospheric cycles of nitrogenous trace compounds for the Northern and Southern Hemispheres are discussed. Source strengths and destruction rates for the nitrogen oxides: NO, NO2 and HNO3 -(NOX) and ammonia (NH3) are given as a function of latitude over continents and oceans. The global amounts of NOX-N and NH3-N produced annually in the period 1950 to 1975 (34 + 5 x one trillion g NOx-N/yr and 29 + or - 6 x one trillion g NH3-N/yr) are much less than previously assumed. Globally, natural and anthropogenic emissions are of similar magnitude. The NOx emission from anthropogenic sources is 1.5 times that from natural processes in the Northern Hemisphere, whereas in the Southern Hemisphere, it is a factor of 3 or 4 less. More than 80% of atmospheric ammonia seems to be derived from excrements of domestic animals, mostly by bulk deposition: 24 + or - 9 x one trillion g NO3 -N/yr and 21 + or - 9 x one trillion g NH4+-N/yr. Another fraction may be removed by absorption on vegetation and soils
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Recent advances in the development of a European Mars climate model in Oxford
Since the early 1990s, efforts have been under way in Oxford to develop a range of numerical weather and climate prediction models for various studies of the Martian atmosphere and near-surface environment. Early versions of the Oxford model were more in the way of 'process models', aimed at relatively idealised studies e.g. of baroclinic instability[1] and low-level western boundary currents in the cross-equatorial solsticial Hadley circulation[2]. Since the mid-1990s, however, the group in Oxford have worked closely with the modelling group at LMD in Paris to develop a joint suite of more sophisticated and comprehensive numerical models of Mars' atmosphere. This collaboration, partly sponsored in recent years by the European Space Agency in connection with the associated development of a climate database for Mars[3], culminated in a suite of global circulation models[4], in which both groups share a library of parametrisation schemes, but in which the Oxford team use a spectral representation of horizontal fields (in the form of spherical harmonics) and the LMD group use a grid-point finite difference representation. These models were described in some detail by Forget et al.[4], and their preliminary validation and use in the construction of first versions of the European Mars Climate Database by Lewis et al.[3]. In the present report, we will review further developments which have taken place since the latter papers were published. Aspects of these developments which are common to both the LMD and Oxford groups will also be covered in the companion contribution by Forget et al. in this meeting, and so will only be touched on briefly here. Instead, we will concentrate on those advances which are more specific to the Oxford version of the model. In the following sections, we outline the main new developments to the model formulation since 1999. Subsequent sections then describe some recent examples where the new model is being utilised to advance a diverse range of studies of Mars atmospheric science
Percolation Systems away from the Critical Point
This article reviews some effects of disorder in percolation systems even
away from the critical density p_c. For densities below p_c, the statistics of
large clusters defines the animals problem. Its relation to the directed
animals problem and the Lee-Yang edge singularity problem is described. Rare
compact clusters give rise to Griffiths singuraties in the free energy of
diluted ferromagnets, and lead to a very slow relaxation of magnetization. In
biassed diffusion on percolation clusters, trapping in dead-end branches leads
to asymptotic drift velocity becoming zero for strong bias, and very slow
relaxation of velocity near the critical bias field.Comment: Minor typos fixed. Submitted to Praman
Frequency-dependent (ac) Conduction in Disordered Composites: a Percolative Study
In a recent paper [Phys. Rev. B{\bf57}, 3375 (1998)], we examined in detail
the nonlinear (electrical) dc response of a random resistor cum tunneling bond
network (, introduced by us elsewhere to explain nonlinear response of
metal-insulator type mixtures). In this work which is a sequel to that paper,
we consider the ac response of the -based correlated () model.
Numerical solutions of the Kirchoff's laws for the model give a power-law
exponent (= 0.7 near ) of the modulus of the complex ac conductance at
moderately low frequencies, in conformity with experiments on various types of
disordered systems. But, at very low frequencies, it gives a simple quadratic
or linear dependence on the frequency depending upon whether the system is
percolating or not. We do also discuss the effective medium approximation
() of our and the traditional random network model, and discuss
their comparative successes and shortcomings.Comment: Revised and reduced version with 17 LaTeX pages plus 8 JPEG figure
Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis
First published online: September 20, 2013BACKGROUND:
Improving our understanding of the relationship between the genotype and the drug resistance phenotype of Mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. Studies that use direct genetic manipulation to identify the mutations that cause M. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutation's contribution to the drug resistance phenotype.
METHODS:
We systematically reviewed the literature for publications reporting allelic exchange experiments in any of the resistance-associated M. tuberculosis genes. We included studies that introduced single point mutations using specialized linkage transduction or site-directed/in vitro mutagenesis and documented a change in the resistance phenotype.
RESULTS:
We summarize evidence supporting the causal relationship of 54 different mutations in eight genes (katG, inhA, kasA, embB, embC, rpoB, gyrA and gyrB) and one intergenic region (furA-katG) with resistance to isoniazid, the rifamycins, ethambutol and fluoroquinolones. We observed a significant role for the strain genomic background in modulating the resistance phenotype of 21 of these mutations and found examples of where the same drug resistance mutations caused varying levels of resistance to different members of the same drug class.
CONCLUSIONS:
This systematic review highlights those mutations that have been shown to causally change phenotypic resistance in M. tuberculosis and brings attention to a notable lack of allelic exchange data for several of the genes known to be associated with drug resistance.This work was supported by the Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to H. N.-G.), the National Institutes of Health/Fogarty International Center (1K01 TW009213 to K.R.J.), departmental funds of the pulmonary division of Massachusetts General Hospital to M. R. F. and the National Institutes of Health/NIAID (U19 A1076217 to M.B.M.)
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
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Pancreatic cancer: Surgery is a feasible therapeutic option for elderly patients
<p>Abstract</p> <p>Background</p> <p>Compromised physiological reserve, comorbidities, and the natural history of pancreatic cancer may deny pancreatic resection from elderly patients. We evaluated outcomes of elderly patients amenable to pancreatic surgery.</p> <p>Methods</p> <p>The medical records of all patients who underwent pancreatic resection at our institution (1995-2007) were retrospectively reviewed. Patient, tumor, and outcomes characteristics in elderly patients aged ≥ 70 years were compared to a younger cohort (<70y).</p> <p>Results</p> <p>Of 460 patients who had surgery for pancreatic neoplasm, 166 (36%) aged ≥ 70y. Compared to patients < 70y (n = 294), elderly patients had more associated comorbidities; 72% vs. 43% (p = 0.01) and a higher rate of malignant pathologies; 73% vs. 59% (p = 0.002). Operative time and blood products consumption were comparable; however, elderly patients had more post-operative complications (41% vs. 29%; p = 0.01), longer hospital stay (26.2 vs. 19.7 days; p < 0.0001), and a higher incidence of peri-operative mortality (5.4% vs. 1.4%; p = 0.01). Multivariable analysis identified age ≥ 70y as an independent predictor of shorter disease-specific survival (DSS) among patients who had surgery for pancreatic adenocarcinoma (n = 224). Median DSS for patients aged ≥ 70y vs. < 70y were 15 months (SE: 1.6) vs. 20 months (SE: 3.4), respectively (p = 0.05). One, two, and 5-Y DSS rates for the cohort of elderly patients were 58%, 36% and 23%, respectively.</p> <p>Conclusions</p> <p>Properly selected elderly patients can undergo pancreatic resection with acceptable post-operative morbidity and mortality rates. Long term survival is achievable even in the presence of adenocarcinoma and therefore surgery should be seriously considered in these patients.</p
The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus are not downregulated in productively infected cells
<p>Abstract</p> <p>Background</p> <p>Over the last several decades it has been noted, using a variety of different methods, that cells infected by a specific gammaretrovirus are resistant to infection by other retroviruses that employ the same receptor; a phenomenon termed receptor interference. Receptor masking is thought to provide an earlier means of blocking superinfection, whereas receptor down regulation is generally considered to occur in chronically infected cells.</p> <p>Results</p> <p>We used replication-competent GFP-expressing viruses containing either an amphotropic murine leukemia virus (A-MLV) or the gibbon ape leukemia virus (GALV) envelope. We also constructed similar viruses containing fluorescence-labeled Gag proteins for the detection of viral particles. Using this repertoire of reagents together with a wide range of antibodies, we were able to determine the presence and availability of viral receptors, and detect viral envelope proteins and particles presence on the cell surface of chronically infected cells.</p> <p>Conclusions</p> <p>A-MLV or GALV receptors remain on the surface of chronically infected cells and are detectable by respective antibodies, indicating that these receptors are not downregulated in these infected cells as previously proposed. We were also able to detect viral envelope proteins on the infected cell surface and infected cells are unable to bind soluble A-MLV or GALV envelopes indicating that receptor binding sites are masked by endogenously expressed A-MLV or GALV viral envelope. However, receptor masking does not completely prevent A-MLV or GALV superinfection.</p
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