The effect of cattle slurry in combination with nitrate and the nitrification inhibitor dicyandiamide on in situ nitrous oxide and dinitrogen emissions

peer-reviewedA field study was conducted to determine the effect of the nitrification inhibitor dicyandiamide (DCD) on N2O and N2 emissions after cattle slurry (CS) application in the presence of nitrate (NO3) fertiliser on seven different occasions (between March 2009 and March 2011). N2O emissions from CS in the presence of NO3 fertiliser were very high (0.4–8.7% of applied N) over a 20-day period, under mild moist conditions. Emissions were significantly larger from the CS treatment compared to an NH4+-N source, supplying the same rate of N as in the slurry. This study supports the view that organic fertilisers should not be applied at the same time as nitrate-based fertilisers, as significant increases in N2O emissions occur. The average N2O mole fraction (N2O/(N2O + N2)) over all seven application dates was 0.34 for CSNO3 compared to 0.24 for the NH4ClNO3 treatment, indicating the dominance of N2 emissions. The rate of nitrification in CSNO3 was slower than in NH4ClNO3, and DCD was found to be an effective nitrification inhibitor in both treatments. However, as N2O emissions were found to be predominantly associated with the NO3 pool, the effect of DCD in lowering N2O emissions is limited in the presence of a NO3 fertiliser. To obtain the maximum cost-benefit of DCD in lowering N2O emissions, under mild moist conditions, it should not be applied to a nitrate containing fertiliser (e.g. ammonium nitrate or calcium ammonium nitrate), and therefore the application of DCD should be restricted to ammonium-based organic or synthetic fertilisers.This research was funded by the Irish National Development Plan, through the Research Stimulus Fund (RSF 07 519), administered by the Irish Department of Agriculture, Food and the Marine

Overcoming information reduced data and experimentally uncertain parameters in ptychography with regularized optimization

The overdetermination of the mathematical problem underlying ptychography is reduced by a host of experimentally more desirable settings. Furthermore, reconstruction of the sample-induced phase shift is typically limited by uncertainty in the experimental parameters and finite sample thicknesses. Presented is a conjugate gradient descent algorithm, regularized optimization for ptychography (ROP), that recovers the partially known experimental parameters along with the phase shift, improves resolution by incorporating the multislice formalism to treat finite sample thicknesses, and includes regularization in the optimization process, thus achieving reliable results from noisy data with severely reduced and underdetermined information.Comment: 18 pages, 7 figures, 3 table

Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Background. Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/microL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods. We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/microL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results. Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/microL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions. Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/microL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/microL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold

DNA methylation transcriptionally regulates the putative tumor cell growth suppressor ZNF677 in non-small cell lung cancers

In our study, we investigated the role of ZNF677 in non-small cell lung cancers (NSCLC). By comparing ZNF677 expression in primary tumor (TU) and in the majority of cases also of corresponding non-malignant lung tissue (NL) samples from > 1,000 NSCLC patients, we found tumor-specific downregulation of ZNF677 expression (adjusted p-values < 0.001). We identified methylation as main mechanism for ZNF677 downregulation in NSCLC cells and we observed tumor-specific ZNF677 methylation in NSCLC patients (p < 0.0001). In the majority of TUs, ZNF677 methylation was associated with loss of ZNF677 expression. Moreover, ZNF677 overexpression in NSCLC cells was associated with reduced cell proliferation and cell migration. ZNF677 was identified to regulate expression of many genes mainly involved in growth hormone regulation and interferon signalling. Finally, patients with ZNF677 methylated TUs had a shorter overall survival compared to patients with ZNF677 not methylated TUs (p = 0.013). Overall, our results demonstrate that ZNF677 is trancriptionally regulated by methylation in NSCLCs, suggest that ZNF677 has tumor cell growth suppressing properties in NSCLCs and that ZNF677 methylation might serve as prognostic parameter in these patients

CDH11 Expression is Associated with Survival in Patients with Osteosarcoma

Previous studies have shown that cadherin-11 (CDH11) may be involved in the metastatic process of osteosarcoma. The correlation of the expression levels of CDH11 in osteosarcoma samples with the risk of disease progression and metastasis was examined. Real time qRT-PCR was used to quantify CDH11 expression in a set of newly established osteosarcoma cell lines, 11 primaries and five metastases, compared to the levels in 12 normal osteoblast cell lines established from healthy bone, and also in a set of 10 snap-frozen osteosarcoma samples. In all cases long term clinical follow-up data was available. The CDH11 expression level decreased gradually from the osteoblast to the primary cell lines (p=0.2184) and further to those established from the tumor metastases (p=0.0275). Importantly, the level of CDH11 expression correlated significantly (p=0.01) with patient survival (Kaplan-Meier survival analysis) in both sample sets (p=0.0128 for the cell lines, p=0.0492 for the biopsies). In conclusion, the results indicate that CDH11 may be useful as a prognostic marker of disease progression and survival in osteosarcoma

In vivo imaging and quantitative analysis of leukocyte directional migration and polarization in inflamed tissue

Directional migration of transmigrated leukocytes to the site of injury is a central event in the inflammatory response. Here, we present an in vivo chemotaxis assay enabling the visualization and quantitative analysis of subtype-specific directional motility and polarization of leukocytes in their natural 3D microenvironment. Our technique comprises the combination of i) semi-automated in situ microinjection of chemoattractants or bacteria as local chemotactic stimulus, ii) in vivo near-infrared reflected-light oblique transillumination (RLOT) microscopy for the visualization of leukocyte motility and morphology, and iii) in vivo fluorescence microscopy for the visualization of different leukocyte subpopulations or fluorescence-labeled bacteria. Leukocyte motility parameters are quantified off-line in digitized video sequences using computer-assisted single cell tracking. Here, we show that perivenular microinjection of chemoattractants [macrophage inflammatory protein-1alpha (MIP-1alpha/Ccl3), platelet-activating factor (PAF)] or E. coli into the murine cremaster muscle induces target-oriented intravascular adhesion and transmigration as well as polarization and directional interstitial migration of leukocytes towards the locally administered stimuli. Moreover, we describe a crucial role of Rho kinase for the regulation of directional motility and polarization of transmigrated leukocytes in vivo. Finally, combining in vivo RLOT and fluorescence microscopy in Cx3CR1(gfp/gfp) mice (mice exhibiting green fluorescent protein-labeled monocytes), we are able to demonstrate differences in the migratory behavior of monocytes and neutrophils.Taken together, we propose a novel approach for investigating the mechanisms and spatiotemporal dynamics of subtype-specific motility and polarization of leukocytes during their directional interstitial migration in vivo

Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects

ABSTRACT Background Reaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD. Method A total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6-18, performed a four-choice RT task with baseline and fast-incentive conditions. Results ADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60-70%. Conclusions The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADH

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1

Toxic proteinaceous deposits and alterations in excitability and activity levels characterize vulnerable neuronal populations in neurodegenerative diseases. Using in vivo two-photon imaging in behaving spino-cerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory cir-cuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compro-mising sensorimotor signals in the cerebellum at early stages. Mutant MLINs express abnormally elevated parvalbumin, harbor high excitatory-to-inhibitory synaptic density, and display more numerous synaptic connections on PNs, indicating an excitation/inhibition imbalance. Chemogenetic inhibition of hyperexcit-able MLINs normalizes parvalbumin expression and restores calcium signaling in Sca1 PNs. Chronic inhibi-tion of mutant MLINs delayed PN degeneration, reduced pathology, and ameliorated motor deficits in Sca1 mice. Conserved proteomic signature of Sca1 MLINs, shared with human SCA1 interneurons, involved the higher expression of FRRS1L, implicated in AMPA receptor trafficking. We thus propose that circuit-level def-icits upstream of PNs are one of the main disease triggers in SCA1

Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA

The multiplicity structure of the hadronic system X produced in deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant mass M_X of the system X. Results are presented on multiplicity distributions and multiplicity moments, rapidity spectra and forward-backward correlations in the centre-of-mass system of X. The data are compared to results in e+e- annihilation, fixed-target lepton-nucleon collisions, hadro-produced diffractive final states and to non-diffractive hadron-hadron collisions. The comparison suggests a production mechanism of virtual photon dissociation which involves a mixture of partonic states and a significant gluon content. The data are well described by a model, based on a QCD-Regge analysis of the diffractive structure function, which assumes a large hard gluonic component of the colourless exchange at low Q^2. A model with soft colour interactions is also successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first submission - omitted bibliograph