Dust sources and deposition during the last glacial maximum and current climate: a comparison of model results with paleodata from ice cores and marine sediments

Mineral dust aerosols in the atmosphere have the potential to affect the global climate by influencing the radiative balance of the atmosphere and the supply of micronutrients to the ocean. Ice and marine sediment cores indicate that dust deposition from the atmosphere was at some locations 2–20 times greater during glacial periods, raising the possibility that mineral aerosols might have contributed to climate change on glacial-interglacial time scales. To address this question, we have used linked terrestrial biosphere, dust source, and atmospheric transport models to simulate the dust cycle in the atmosphere for current and last glacial maximum (LGM) climates. We obtain a 2.5-fold higher dust loading in the entire atmosphere and a twenty-fold higher loading in high latitudes, in LGM relative to present. Comparisons to a compilation of atmospheric dust deposition flux estimates for LGM and present in marine sediment and ice cores show that the simulated flux ratios are broadly in agreement with observations; differences suggest where further improvements in the simple dust model could be made. The simulated increase in high-latitude dustiness depends on the expansion of unvegetated areas, especially in the high latitudes and in central Asia, caused by a combination of increased aridity and low atmospheric [CO2]. The existence of these dust source areas at the LGM is supported by pollen data and loess distribution in the northern continents. These results point to a role for vegetation feedbacks, including climate effects and physiological effects of low [CO2], in modulating the atmospheric distribution of dust.

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the mammary gland of lactating dairy cows

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the mammary gland of the lactating dairy cow is constructed and solved in the steady state. The model contains four intracellular and four extracellular pools and conservation of mass principles are applied to generate the fundamental equations describing the behaviour of the system. The experimental measurements required for model solution are milk secretion and plasma flow rate across the gland in combination with phenylalanine and tyrosine concentrations and plateau isotopic enrichments in arterial and venous plasma and free and protein bound milk during a constant infusion of [1-(13)C]phenylalanine and [2,3,5,6-(2)H]tyrosine tracer. If assumptions are made, model solution enables determination of steady state flows for phenylalanine and tyrosine inflow to the gland, outflow from it and bypass, and flows representing the synthesis and degradation of constitutive protein and hydroxylation. The model is effective in providing information about the fates of phenylalanine and tyrosine in the mammary gland and could be used as part of a more complex system describing amino acid metabolism in the whole ruminant.

How well can we model stream phosphorus concentrations in agricultural catchments?

Mechanistic catchment-scale phosphorus models appear to perform poorly where diffuse sources dominate. We investigate the reasons for this for one model, INCA-P, testing model output against 18 months of daily data in a small Scottish catchment. We examine key model processes and provide recommendations for model improvement and simplification. Improvements to the particulate phosphorus simulation are especially needed. The model evaluation procedure is then generalised to provide a checklist for identifying why model performance may be poor or unreliable, incorporating calibration, data, structural and conceptual challenges. There needs to be greater recognition that current models struggle to produce positive Nash–Sutcliffe statistics in agricultural catchments when evaluated against daily data. Phosphorus modelling is difficult, but models are not as useless as this might suggest. We found a combination of correlation coefficients, bias, a comparison of distributions and a visual assessment of time series a better means of identifying realistic simulations.

A new understanding of El Niño's impact over East Asia: dominance of the ENSO combination mode

Previous studies have shown that the Indo-Pacific atmospheric response to ENSO comprises two dominant modes of variability: a meridionally quasi-symmetric response (independent from the annual cycle) and an anti-symmetric response (arising from the nonlinear atmospheric interaction between ENSO variability and the annual cycle), referred to as the combination mode (C-Mode). This study demonstrates that the direct El Niño signal over the tropics is confined to the equatorial region and has no significant impact on the atmospheric response over East Asia. The El Niño-associated equatorial anomalies can be expanded towards off-equatorial regions by the C-Mode through ENSO’s interaction with the annual cycle. The C-Mode is the prime driver for the development of an anomalous low-level anticyclone over the western North Pacific (WNP) during the El Niño decay phase, which usually transports more moisture to East Asia and thereby causes more precipitation over southern China. We use an Atmospheric General Circulation Model that well reproduces the WNP anticyclonic anomalies when both El Niño sea surface temperature (SST) anomalies as well as the SST annual cycle are prescribed as boundary conditions. However, no significant WNP anticyclonic circulation anomaly appears during the El Niño decay phase when excluding the SST annual cycle. Our analyses of observational data and model experiments suggest that the annual cycle plays a key role in the East Asian climate anomalies associated with El Niño through their nonlinear atmospheric interaction. Hence, a realistic simulation of the annual cycle is crucial in order to correctly capture the ENSO-associated climate anomalies over East Asia.

Mathematical model for NF-kappaB-driven proliferation of adult neural stem cells

Neural stem cells (NSCs) are early precursors of neuronal and glial cells. NSCs are capable of generating identical progeny through virtually unlimited numbers of cell divisions (cell proliferation), producing daughter cells committed to differentiation. Nuclear factor kappa B (NF-kappaB) is an inducible, ubiquitous transcription factor also expressed in neurones, glia and neural stem cells. Recently, several pieces of evidence have been provided for a central role of NF-kappaB in NSC proliferation control. Here, we propose a novel mathematical model for NF-kappaB-driven proliferation of NSCs. We have been able to reconstruct the molecular pathway of activation and inactivation of NF-kappaB and its influence on cell proliferation by a system of nonlinear ordinary differential equations. Then we use a combination of analytical and numerical techniques to study the model dynamics. The results obtained are illustrated by computer simulations and are, in general, in accordance with biological findings reported by several independent laboratories. The model is able to both explain and predict experimental data. Understanding of proliferation mechanisms in NSCs may provide a novel outlook in both potential use in therapeutic approaches, and basic research as well.

Projected changes in tropical cyclones over Vietnam and the South China Sea using a 25 km regional climate model perturbed physics ensemble

The regional climate modelling system PRECIS, was run at 25 km horizontal resolution for 150 years (1949-2099) using global driving data from a five member perturbed physics ensemble (based on the coupled global climate model HadCM3). Output from these simulations was used to investigate projected changes in tropical cyclones (TCs) over Vietnam and the South China Sea due to global warming (under SRES scenario A1B). Thirty year climatological mean periods were used to look at projected changes in future (2069-2098) TCs compared to a 1961-1990 baseline. Present day results were compared qualitatively with IBTrACS observations and found to be reasonably realistic. Future projections show a 20-44 % decrease in TC frequency, although the spatial patterns of change differ between the ensemble members, and an increase of 27-53 % in the amount of TC associated precipitation. No statistically significant changes in TC intensity were found, however, the occurrence of more intense TCs (defined as those with a maximum 10 m wind speed > 35 m/s) was found to increase by 3-9 %. Projected increases in TC associated precipitation are likely caused by increased evaporation and availability of atmospheric water vapour, due to increased sea surface and atmospheric temperature. The mechanisms behind the projected changes in TC frequency are difficult to link explicitly; changes are most likely due to the combination of increased static stability, increased vertical wind shear and decreased upward motion, which suggest a decrease in the tropical overturning circulation.

Sahel decadal rainfall variability and the role of model horizontal resolution

Substantial low-frequency rainfall fluctuations occurred in the Sahel throughout the twentieth century, causing devastating drought. Modeling these low-frequency rainfall fluctuations has remained problematic for climate models for many years. Here we show using a combination of state-of-the-art rainfall observations and high-resolution global climate models that changes in organized heavy rainfall events carry most of the rainfall variability in the Sahel at multiannual to decadal time scales. Ability to produce intense, organized convection allows climate models to correctly simulate the magnitude of late-twentieth century rainfall change, underlining the importance of model resolution. Increasing model resolution allows a better coupling between large-scale circulation changes and regional rainfall processes over the Sahel. These results provide a strong basis for developing more reliable and skilful long-term predictions of rainfall (seasons to years) which could benefit many sectors in the region by allowing early adaptation to impending extremes.

Interactions between wind-blown snow redistribution and melt ponds in a coupled ocean–sea ice model

Introducing a parameterization of the interactions between wind-driven snow depth changes and melt pond evolution allows us to improve large scale models. In this paper we have implemented an explicit melt pond scheme and, for the first time, a wind dependant snow redistribution model and new snow thermophysics into a coupled ocean–sea ice model. The comparison of long-term mean statistics of melt pond fractions against observations demonstrates realistic melt pond cover on average over Arctic sea ice, but a clear underestimation of the pond coverage on the multi-year ice (MYI) of the western Arctic Ocean. The latter shortcoming originates from the concealing effect of persistent snow on forming ponds, impeding their growth. Analyzing a second simulation with intensified snow drift enables the identification of two distinct modes of sensitivity in the melt pond formation process. First, the larger proportion of wind-transported snow that is lost in leads directly curtails the late spring snow volume on sea ice and facilitates the early development of melt ponds on MYI. In contrast, a combination of higher air temperatures and thinner snow prior to the onset of melting sometimes make the snow cover switch to a regime where it melts entirely and rapidly. In the latter situation, seemingly more frequent on first-year ice (FYI), a smaller snow volume directly relates to a reduced melt pond cover. Notwithstanding, changes in snow and water accumulation on seasonal sea ice is naturally limited, which lessens the impacts of wind-blown snow redistribution on FYI, as compared to those on MYI. At the basin scale, the overall increased melt pond cover results in decreased ice volume via the ice-albedo feedback in summer, which is experienced almost exclusively by MYI.

Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.

The Bone Formation Capabilities of the Anorganic Bone Matrix-Synthetic Cell-Binding Peptide 15 Grafts in an Animal Periodontal Model: A Histologic and Histomorphometric Study in Dogs

Background: The aim of this study is to verify the regenerative potential of particulate anorganic bone matrix synthetic peptide-15 (ABM-P-15) in class III furcation defects associated or not with expanded polytetrafluoroethylene membranes. Methods: Class III furcation defects were produced in the mandibular premolars (P2, P3, and P4) of six dogs and filled with impression material. The membranes and the bone grafts were inserted into P3 and P4, which were randomized to form the test and control groups, respectively; P2 was the negative control group. The animals were sacrificed 3 months post-treatment. Results: Histologically, the complete closure of class III furcation defects was not observed in any of the groups. Partial periodontal regeneration with similar morphologic characteristics among the groups was observed, however, through the formation of new cementum, periodontal ligament, and bone above the notch. Histologic analysis showed granules from the bone graft surrounded by immature bone matrix and encircled by newly formed tissue in the test group. The new bone formation area found in the negative control group was 2.28 +/- 2.49 mm(2) and in the test group it was 6.52 +/- 5.69 mm(2), which showed statistically significant differences for these groups considering this parameter (Friedman test P <0.05). There was no statistically significant difference among the negative control, control, and test groups for the other parameters. Conclusions: The regenerative potential of ABM-P-15 was demonstrated through new bone formation circumscribing and above the graft particles. The new bone also was accompanied by the formation of new cementum and periodontal ligament fibers. J Periodontol 2010;81:594-603.

Combination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease in Immunodeficient Mice Caused by Fluconazole-resistant Cryptococcus neoformans

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 x 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.

A DNA Vaccine Encoding the Enterohemorragic Escherichia coli Shiga-Like Toxin 2 A(2) and B Subunits Confers Protective Immunity to Shiga Toxin Challenge in the Murine Model

Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A(1) peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A(2) peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2 Delta AB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A(2) sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte-macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2 Delta AB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae.

Correlation of the in vitro antifungal drug susceptibility with the in vivo activity of fluconazole in a murine model of cerebral infection caused by Cryptococcus gattii

Forty Cryptococcus gattii strains were submitted to antifungal susceptibility testing with fluconazole, itraconazole, amphotericin B and terbinafine. The minimum inhibitory concentration (MIC) ranges were 0.5-64.0 for fluconazole, < 0.015-0.25 for itraconazole, 0.015-0.5 for amphotericin B and 0.062-2.0 for terbinafine. A bioassay for the quantitation of fluconazole in murine brain tissue was developed. Swiss mice received daily injections of the antifungal, and their brains were withdrawn at different times over the 14-day study period. The drug concentrations varied from 12.98 to 44.60 mu g/mL. This assay was used to evaluate the therapy with fluconazole in a model of infection caused by C. gattii. Swiss mice were infected intracranially and treated with fluconazole for 7, 10 or 14 days. The treatment reduced the fungal burden, but an increase in fungal growth was observed on day 14. The MIC for fluconazole against sequential isolates was 16 mu g/mL, except for the isolates obtained from animals treated for 14 days (MIC = 64 mu g/mL). The quantitation of cytokines revealed a predominance of IFN-gamma and IL-12 in the non-treated group and elevation of IL-4 and IL-10 in the treated group. Our data revealed the possibility of acquired resistance during the antifungal drug therapy.

Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression

Background: Gamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA) osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo. Methods: Established C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD) counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR. Results: GLA caused a significant decrease in tumour size (75 +/- 8.8%) and reduced MVD by 44 +/- 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF) (71 +/- 16%) and the VEGF receptor Flt1 (57 +/- 5.8%) but not Flk1. Expression of ERK1/2 was also reduced by 27 +/- 7.7% and 31 +/- 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2) was reduced by 35 +/- 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 +/- 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 +/- 18%) while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 +/- 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 +/- 7.3%) while p21 remained unchanged. The expression of p53 was increased (44 +/- 16%) by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 +/- 11%) of BrdU incorporation into the tumour in vivo. Conclusion: Overall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein expression of VEGF, Flt1, ERK1, ERK2, MMP2, Cyclin D1, pRb, p53 and p27. Combination therapy using drugs with other, complementary targets and GLA could lead to gains in treatment efficacy in this notoriously difficult to treat tumour.

Static Hopfions in the extended Skyrme-Faddeev model

We construct static soliton solutions with non-zero Hopf topological charges to a theory which is an extension of the Skyrme-Faddeev model by the addition of a further quartic term in derivatives. We use an axially symmetric ansatz based on toroidal coordinates, and solve the resulting two coupled non-linear partial differential equations in two variables by a successive over-relaxation (SOR) method. We construct numerical solutions with Hopf charge up to four, and calculate their analytical behavior in some limiting cases. The solutions present an interesting behavior under the changes of a special combination of the coupling constants of the quartic terms. Their energies and sizes tend to zero as that combination approaches a particular special value. We calculate the equivalent of the Vakulenko and Kapitanskii energy bound for the theory and find that it vanishes at that same special value of the coupling constants. In addition, the model presents an integrable sector with an in finite number of local conserved currents which apparently are not related to symmetries of the action. In the intersection of those two special sectors the theory possesses exact vortex solutions (static and time dependent) which were constructed in a previous paper by one of the authors. It is believed that such model describes some aspects of the low energy limit of the pure SU(2) Yang-Mills theory, and our results may be important in identifying important structures in that strong coupling regime.