Soil Aggregation, Organic Carbon Concentration, and Soil Bulk Density As Affected by Cover Crop Species in a No-Tillage System

Soil aggregation and the distribution of total organic carbon (TOC) may be affected by soil tillage and cover crops. The objective of this study was to determine the effects of crop rotation with cover crops on soil aggregation, TOC concentration in the soil aggregate fractions, and soil bulk density under a no-tillage system (NTS) and conventional tillage system (CTS, one plowing and two disking). This was a three-year study with cover crop/rice/cover crop/rice rotations in the Brazilian Cerrado. A randomized block experimental design with six treatments and three replications was used. The cover crops (treatments) were: fallow, Panicum maximum, Brachiaria ruziziensis, Brachiaria brizantha, and millet (Pennisetum glaucum). An additional treatment, fallow plus CTS, was included as a control. Soil samples were collected at the depths of 0.00-0.05 m, 0.05-0.10 m, and 0.10-0.20 m after the second rice harvest. The treatments under the NTS led to greater stability in the soil aggregates (ranging from 86.33 to 95.37 %) than fallow plus CTS (ranging from 74.62 to 85.94 %). Fallow plus CTS showed the highest number of aggregates smaller than 2 mm. The cover crops affected soil bulk density differently, and the millet treatment in the NTS had the lowest values. The cover crops without incorporation provided the greatest accumulation of TOC in the soil surface layers. The TOC concentration was positively correlated with the aggregate stability index in all layers and negatively correlated with bulk density in the 0.00-0.10 m layer.

Native folding of aggregation-prone recombinant proteins in Escherichia coli by osmolytes, plasmid- or benzyl alcohol-overexpressed molecular chaperones.

When massively expressed in bacteria, recombinant proteins often tend to misfold and accumulate as soluble and insoluble nonfunctional aggregates. A general strategy to improve the native folding of recombinant proteins is to increase the cellular concentration of viscous organic compounds, termed osmolytes, or of molecular chaperones that can prevent aggregation and can actively scavenge and convert aggregates into natively refoldable species. In this study, metal affinity purification (immobilized metal ion affinity chromatography [IMAC]), confirmed by resistance to trypsin digestion, was used to distinguish soluble aggregates from soluble nativelike proteins. Salt-induced accumulation of osmolytes during induced protein synthesis significantly improved IMAC yields of folding-recalcitrant proteins. Yet, the highest yields were obtained with cells coexpressing plasmid-encoded molecular chaperones DnaK-DnaJ-GrpE, ClpB, GroEL-GroES, and IbpA/B. Addition of the membrane fluidizer heat shock-inducer benzyl alcohol (BA) to the bacterial medium resulted in similar high yields as with plasmid-mediated chaperone coexpression. Our results suggest that simple BA-mediated induction of endogenous chaperones can substitute for the more demanding approach of chaperone coexpression. Combined strategies of osmolyte-induced native folding with heat-, BA-, or plasmid-induced chaperone coexpression can be thought to optimize yields of natively folded recombinant proteins in bacteria, for research and biotechnological purposes.

Influence of compliance to respiratory weaning consensus conference criteria on respiratory outcome within 48h after planned extubation

INTRODUCTION. A two-step assessment (readiness to wean (RW) followed by spontaneousbreathing trial (SBT)) of predefined criteria is recommended before planned extubation(PE)1.OBJECTIVES. We aimed to evaluate if compliance to all guideline criteria was associatedwith better respiratory outcome within 48 h after PE.METHODS. The data (extracted from our clinical information system) of 458 consecutivepatients who underwent PE after C48 h of invasive ventilation in our medico-surgical ICUwere analyzed. We evaluated compliance with guidelines [1] regarding respiratory rate, tidalvolume, PaO2, FiO2, PEEP, PaCO2, pH, heart rate, systolic arterial pressure and arrhythmiaduringRWand SBT assessment (RW and SBT within 2 h). A patient was classified as RW+ ifallRWcriteria were fulfilled andRW-if at least 1 criterion was violated. The same approachwas used to define SBT+ and SBT- patients. During the 48 h following PE, we assessed theoccurrence of post-PE respiratory failure (PRF) (defined as the presence of at least 1 consensuscriterion of respiratory failure [1]), reintubation (after NIV failure or because of immediateintubation criteria) and cumulative duration of post-PE ventilation (PPEV = Post-PE invasive+ non-invasive ventilation). ICU mortality was recorded. Comparisons for variousoutcomes were performed by Chi-square and t tests.RESULTS. All consensus criteria were fulfilled in 77.3% of the patients during RW and in68.1% of the patients during SBT.[Compliance to weaning criteria and outcome]N = 458 PRF (%) Reintubation (%) PPEV (min) ICU mortality (%)All patients 53.5 10.0 542 ± 664 6.1RW+ 50.0 9.3 490 ± 626 5.4RW- 65.4* 12.5 718 ± 757** 8.7SBT+ 52.6 8.0 498 ± 594 6.7SBT- 55.5 14.4*** 637 ± 788**** 4.8Occurrence of PRF only was not associated with increased ICU mortality: 4.2 versus 7.8%,p = 0.11. By contrast, ICU mortality was significantly increased in patients requiring reintubation:21.7 versus 4.4%. p\0.001; * p = 0.006 RW+ versus RW-; ** p = 0.003RW+ versus RW-; *** p = 0.035 SBT+ versus SBT-; **** p = 0.030 SBT+ versusSBTCONCLUSIONS.In our ICU, compliance to all criteria of the two-step published approach ofrespiratory weaning was not optimal but reintubation rate was comparable to published data.Compliance with consensus conference guidelines was associated with lower reintubation rateand shorter PPEV but not with ICU mortality. As mortality was increased by reintubation,more sensitive and specific criteria to predict the risk of reintubation are probably needed.REFERENCE. Boles JM, et al. Eur Respir J 2007;29:1033-56.

Minimal analytical characterisation of engineered nanomaterials need for hazard assessment in biological matrices

The safe and responsible development of engineered nanomaterials (ENM), nanotechnology-based materials and products, together with the definition of regulatory measures and implementation of "nano"-legislation in Europe require a widely supported scientific basis and sufficient high quality data upon which to base decisions. At the very core of such a scientific basis is a general agreement on key issues related to risk assessment of ENMs which encompass the key parameters to characterise ENMs, appropriate methods of analysis and best approach to express the effect of ENMs in widely accepted dose response toxicity tests. The following major conclusions were drawn: Due to high batch variability of ENMs characteristics of commercially available and to a lesser degree laboratory made ENMs it is not possible to make general statements regarding the toxicity resulting from exposure to ENMs. 1) Concomitant with using the OECD priority list of ENMs, other criteria for selection of ENMs like relevance for mechanistic (scientific) studies or risk assessment-based studies, widespread availability (and thus high expected volumes of use) or consumer concern (route of consumer exposure depending on application) could be helpful. The OECD priority list is focussing on validity of OECD tests. Therefore source material will be first in scope for testing. However for risk assessment it is much more relevant to have toxicity data from material as present in products/matrices to which men and environment are be exposed. 2) For most, if not all characteristics of ENMs, standardized methods analytical methods, though not necessarily validated, are available. Generally these methods are only able to determine one single characteristic and some of them can be rather expensive. Practically, it is currently not feasible to fully characterise ENMs. Many techniques that are available to measure the same nanomaterial characteristic produce contrasting results (e.g. reported sizes of ENMs). It was recommended that at least two complementary techniques should be employed to determine a metric of ENMs. The first great challenge is to prioritise metrics which are relevant in the assessment of biological dose response relations and to develop analytical methods for characterising ENMs in biological matrices. It was generally agreed that one metric is not sufficient to describe fully ENMs. 3) Characterisation of ENMs in biological matrices starts with sample preparation. It was concluded that there currently is no standard approach/protocol for sample preparation to control agglomeration/aggregation and (re)dispersion. It was recommended harmonization should be initiated and that exchange of protocols should take place. The precise methods used to disperse ENMs should be specifically, yet succinctly described within the experimental section of a publication. 4) ENMs need to be characterised in the matrix as it is presented to the test system (in vitro/ in vivo). 5) Alternative approaches (e.g. biological or in silico systems) for the characterisation of ENMS are simply not possible with the current knowledge. Contributors: Iseult Lynch, Hans Marvin, Kenneth Dawson, Markus Berges, Diane Braguer, Hugh J. Byrne, Alan Casey, Gordon Chambers, Martin Clift, Giuliano Elia1, Teresa F. Fernandes, Lise Fjellsbø, Peter Hatto, Lucienne Juillerat, Christoph Klein, Wolfgang Kreyling, Carmen Nickel1, and Vicki Stone.

A probabilistic approach to niche-based community models for spatial forecasts of assemblage properties and their uncertainties

Aim Conservation strategies are in need of predictions that capture spatial community composition and structure. Currently, the methods used to generate these predictions generally focus on deterministic processes and omit important stochastic processes and other unexplained variation in model outputs. Here we test a novel approach of community models that accounts for this variation and determine how well it reproduces observed properties of alpine butterfly communities. Location The western Swiss Alps. Methods We propose a new approach to process probabilistic predictions derived from stacked species distribution models (S-SDMs) in order to predict and assess the uncertainty in the predictions of community properties. We test the utility of our novel approach against a traditional threshold-based approach. We used mountain butterfly communities spanning a large elevation gradient as a case study and evaluated the ability of our approach to model species richness and phylogenetic diversity of communities. Results S-SDMs reproduced the observed decrease in phylogenetic diversity and species richness with elevation, syndromes of environmental filtering. The prediction accuracy of community properties vary along environmental gradient: variability in predictions of species richness was higher at low elevation, while it was lower for phylogenetic diversity. Our approach allowed mapping the variability in species richness and phylogenetic diversity projections. Main conclusion Using our probabilistic approach to process species distribution models outputs to reconstruct communities furnishes an improved picture of the range of possible assemblage realisations under similar environmental conditions given stochastic processes and help inform manager of the uncertainty in the modelling results

Morphology and segregation in two-component diffusion-limited aggregation

A diffusion-limited-aggregation (DLA) model with two components (A and B species) is presented to investigate the structure of the composite deposits. The sticking probability PAB (=PBA) between the different species is introduced into the original DLA model. By using computer simulation it is shown that various patterns are produced with varying the sticking probabilities PAB (=PBA) and PAA (= PBB), where PAA (=PBB) is the sticking probability between the same species. Segregated patterns can be analyzed under the condition PAB < PAA, assumed throughout the paper. With decreasing sticking probability PAB, a clustering of the same species occurs. With sufficiently small values of both sticking probabilities PAB and PAA, the deposit becomes dense and the segregated patterns of the composite deposit show a striped structure. The effect of the concentration on the pattern morphology is also shown.

Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease.

Machado-Joseph disease is the most frequently found dominantly-inherited cerebellar ataxia. Over-repetition of a CAG trinucleotide in the MJD1 gene translates into a polyglutamine tract within the ataxin 3 protein, which upon proteolysis may trigger Machado-Joseph disease. We investigated the role of calpains in the generation of toxic ataxin 3 fragments and pathogenesis of Machado-Joseph disease. For this purpose, we inhibited calpain activity in mouse models of Machado-Joseph disease by overexpressing the endogenous calpain-inhibitor calpastatin. Calpain blockage reduced the size and number of mutant ataxin 3 inclusions, neuronal dysfunction and neurodegeneration. By reducing fragmentation of ataxin 3, calpastatin overexpression modified the subcellular localization of mutant ataxin 3 restraining the protein in the cytoplasm, reducing aggregation and nuclear toxicity and overcoming calpastatin depletion observed upon mutant ataxin 3 expression. Our findings are the first in vivo proof that mutant ataxin 3 proteolysis by calpains mediates its translocation to the nucleus, aggregation and toxicity and that inhibition of calpains may provide an effective therapy for Machado-Joseph disease.

Implementation of raltegravir in routine clinical practice: selection criteria for choosing this drug, virologic response rates, and characteristics of failures.

BACKGROUND: Raltegravir (RAL) achieved remarkable virologic suppression rates in randomized-clinical trials, but today efficacy data and factors for treatment failures in a routine clinical care setting are limited. METHODS: First, factors associated with a switch to RAL were identified with a logistic regression including patients from the Swiss HIV Cohort Study with a history of 3 class failure (n = 423). Second, predictors for virologic outcome were identified in an intent-to-treat analysis including all patients who received RAL. Last observation carried forward imputation was used to determine week 24 response rate (HIV-1 RNA >or= 50 copies/mL). RESULTS: The predominant factor associated with a switch to RAL in patients with suppressed baseline RNA was a regimen containing enfuvirtide [odds ratio 41.9 (95% confidence interval: 11.6-151.6)]. Efficacy analysis showed an overall response rate of 80.9% (152/188), whereas 71.8% (84/117) and 95.8% (68/71) showed viral suppression when stratified for detectable and undetectable RNA at baseline, respectively. Overall CD4 cell counts increased significantly by 42 cells/microL (P < 0.001). Characteristics of failures were a genotypic sensitivity score of the background regimen <or=1, very low RAL plasma concentrations, poor adherence, and high viral load at baseline. CONCLUSIONS: Virologic suppression rates in our routine clinical care setting were promising and comparable with data from previously published randomized-controlled trials.

Recent misconceptions about the "database search problem": a probabilistic analysis using Bayesian networks

This paper analyses and discusses arguments that emerge from a recent discussion about the proper assessment of the evidential value of correspondences observed between the characteristics of a crime stain and those of a sample from a suspect when (i) this latter individual is found as a result of a database search and (ii) remaining database members are excluded as potential sources (because of different analytical characteristics). Using a graphical probability approach (i.e., Bayesian networks), the paper here intends to clarify that there is no need to (i) introduce a correction factor equal to the size of the searched database (i.e., to reduce a likelihood ratio), nor to (ii) adopt a propositional level not directly related to the suspect matching the crime stain (i.e., a proposition of the kind 'some person in (outside) the database is the source of the crime stain' rather than 'the suspect (some other person) is the source of the crime stain'). The present research thus confirms existing literature on the topic that has repeatedly demonstrated that the latter two requirements (i) and (ii) should not be a cause of concern.

Development of an aggregation assay to screen FimH antagonists.

Alpha-D-mannopyranosides are potent FimH antagonists, which inhibit the adhesion of Escherichia coli to highly mannosylated uroplakin Ia on the urothelium and therefore offer an efficient therapeutic opportunity for the treatment and prevention of urinary tract infection. For the evaluation of the therapeutic potential of FimH antagonists, their effect on the disaggregation of E. coli from Candida albicans and guinea pig erythrocytes (GPE) was studied. The mannose-specific binding of E. coli to yeast cells and erythrocytes is mediated by type 1 pili and can be monitored by aggregometry. Maximal aggregation of C. albicans or GPE to E. coli is reached after 600 s. Then the FimH antagonist was added and disaggregation determined by light transmission over a period of 1400 s. A FimH-deleted mutant of E. coli, which does not induce any aggregation, was used in a control experiment. The activities of FimH antagonists are expressed as IC(50)s, the half maximal inhibitory concentration of the disaggregation potential. n-Heptyl alpha-D-mannopyranoside (1) was used as a reference compound and exhibits an IC(50) of 77.14 microM , whereas methyl alpha-D-mannopyranoside (2) does not lead to any disaggregation at concentrations up to 800 microM. o-Chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl alpha-D-mannopyranoside (3) shows a 90-fold and 2-chloro-4-nitrophenyl alpha-D-mannopyranoside (4) a 6-fold increased affinity compared to 1. Finally, 4-nitrophenyl alpha-D-mannopyranoside (5) exhibits an activity similar to 1. As negative control, D-galactose (6) was used. The standardized aggregation assay generates concentration-dependent, reproducible data allowing the evaluation of FimH antagonists according to their potency to inhibit E. coli adherence and can therefore be employed to select candidates for experimental and clinical studies for treatment and prevention of urinary tract infections.

Analysis of Existing Work-Zone Devices with MASH Safety Performance Criteria, TPF-5(018), 2009

Crashworthy, work-zone, portable sign support systems accepted under NCHRP Report No. 350 were analyzed to predict their safety peformance according to the TL-3 MASH evaluation criteria. An analysis was conducted to determine which hardware parameters of sign support systems would likely contribute to the safety performance with MASH. The acuracy of the method was evaluated through full-scale crash testing. Four full-scale crash tests were conducted with a pickup truck. Two tall-mounted, sign support systems with aluminum sign panels failed the MASH criteria due to windshield penetration. One low-mounted system with a vinyl, roll-up sign panel failed the MASH criteria due to windshield and floorboard penetration. Another low-mounted system with an aluminum sign panel successfully met the MASH criteria. Four full-scale crash tests were conducted with a small passenger car. The low-mounted tripod system with an aluminum sign panel failed the MASH criteria due to windshield penetration. One low-mounted system with aluminum sign panel failed the MASH criteria due to excessive windshield deformation, and another similar system passed the MASH criteria. The low-mounted system with a vinyl, roll-up sign panel successfully met the MASH criteria. Hardware parameters of work-zone sign support systems that were determined to be important for failure with MASH include sign panel material, the height to the top of the mast, the presence of flags, sign-locking mechanism, base layout and system orientation. Flowcharts were provided to assist manufacturers when designing new sign support systems.

First explicit criteria to decide on the appropriateness of therapy of ulcerative colitis: the European EPATUC panel

Background: Ulcerative colitis (UC) is a chronic disease with a wide variety of treatment options many of which are not evidence based. Supplementing available guidelines, which are often broadly defined, consensus-based and generally not tailored to specifically reflect the individual patient situation, we developed explicit appropriateness criteria to assist, and improve treatment decisions. Methods: We used the RAND appropriateness method which does not force consensus. An extensive literature review was compiled based on and supplementing, where necessary, the ECCO UC 2011 guidelines. EPATUC (endorsed by ECCO) was formed by 7 gastroenterologists, 2 surgeons and 2 general practitioners from throughout Europe. Clinical scenarios reflecting practice were rated on a 9-point scale from 1 (extremely inappropriate) to 9 (extremely appropriate), based on the expert's experience and the available literature. After extensive discussion, all scenarios were re-rated at a two-day panel meeting. Median and disagreement (D) were used to categorize ratings into 3 categories: appropriate (A), uncertain (U) and inappropriate (I). Results: 718 clinical scenarios were rated, structured in 13 main clinical presentations: not refractory (n = 64) or refractory (n = 33) proctitis, mild to moderate left-sided (n = 72) or extensive (n = 48) colitis, severe colitis (n = 36), steroid- dependant colitis (n = 36), steroid-refractory colitis (n = 55), acute pouchitis (n = 96), maintenance of remission (n = 248), colorectal cancer prevention (n = 9) and fulminant colitis (n = 9). Overall, 100 indications were judged appropriate (14%), 129 uncertain (18%) and 489 inappropriate (68%). Disagreement between experts was very low (6%). Conclusions: For the very first time, explicit appropriateness criteria for therapy of UC were developed that allow both specific and rapid therapeutic decision making and prospective assessment of treatment appropriateness. Comparison of these detailed scenarios with patient profiles encountered in the Swiss IBD cohort study indicates good concordance. EPATUC criteria will be freely accessible on the internet (epatuc.ch)

Criteria for hitting probabilities with applications to systems of stochastic wave equations

We develop several results on hitting probabilities of random fields which highlight the role of the dimension of the parameter space. This yields upper and lower bounds in terms of Hausdorff measure and Bessel-Riesz capacity, respectively. We apply these results to a system of stochastic wave equations in spatial dimension k >- 1 driven by a d-dimensional spatially homogeneous additive Gaussian noise that is white in time and colored in space.