Early expression of antiinsulin autoantibodies of humans and the NOD mouse: Evidence for early determination of subsequent diabetes

With the development of an insulin autoantibody (IAA) assay performed in 96-well filtration plates, we have evaluated prospectively the development of IAA in NOD mice (from 4 weeks of age) and children (from 7 to 10 months of age) at genetic risk for the development of type 1 diabetes. NOD mice had heterogeneous expression of IAA despite being inbred. IAA reached a peak between 8 and 16 weeks and then declined. IAA expression by NOD mice at 8 weeks of age was strongly associated with early development of diabetes, which occurred at 16–18 weeks of age (NOD mice IAA+ at 8 weeks: 83% (5/6) diabetic by 18 weeks versus 11% (1/9) of IAA negative at 8 weeks; P < .01). In man, IAA was frequently present as early as 9 months of age, the first sampling time. Of five children found to have persistent IAA before 1 year of age, four have progressed to diabetes (all before 3.5 years of age) and the fifth is currently less than age 2. Of the 929 children not expressing persistent IAA before age 1, only one has progressed to diabetes to date (age onset 3), and this child expressed IAA at his second visit (age 1.1). In new onset patients, the highest levels of IAA correlated with an earlier age of diabetes onset. Our data suggest that the program for developing diabetes of NOD mice and humans is relatively “fixed” early in life and, for NOD mice, a high risk of early development of diabetes is often determined by 8 weeks of age. With such early determination of high risk of progression to diabetes, immunologic therapies in humans may need to be tested in children before the development of IAA for maximal efficacy.

Measurement of genetic structure within populations using Moran's spatial autocorrelation statistics.

Spatial structure of genetic variation within populations, an important interacting influence on evolutionary and ecological processes, can be analyzed in detail by using spatial autocorrelation statistics. This paper characterizes the statistical properties of spatial autocorrelation statistics in this context and develops estimators of gene dispersal based on data on standing patterns of genetic variation. Large numbers of Monte Carlo simulations and a wide variety of sampling strategies are utilized. The results show that spatial autocorrelation statistics are highly predictable and informative. Thus, strong hypothesis tests for neutral theory can be formulated. Most strikingly, robust estimators of gene dispersal can be obtained with practical sample sizes. Details about optimal sampling strategies are also described.

Growth, survival, gene expression, microbiota and tryptic activity during feeding of Scophthalmus maximus first feeding larvae with beta-glucan (MacroGard)

Reflecting the natural biology of mass spawning fish aquaculture production of fish larvae is often hampered by high and unpredictable mortality rates. The present study aimed to enhance larval performance and immunity via the oral administration of an immunomodulator, beta-glucan (MacroGard®) in turbot (Scophthalmus maximus). Rotifers (Brachionus plicatilis) were incubated with or without yeast beta-1,3/1,6-glucan in form of MacroGard® at a concentration of 0.5 g/L. Rotifers were fed to first feeding turbot larvae once a day. From day 13 dph onwards all tanks were additionally fed untreated Artemia sp. nauplii (1 nauplius ml/L). Daily mortality was monitored and larvae were sampled at 11 and 24 dph for expression of 30 genes, trypsin activity and size measurements. Along with the feeding of beta-glucan daily mortality was significantly reduced by ca. 15% and an alteration of the larval microbiota was observed. At 11 dph gene expression of trypsin and chymotrypsin was elevated in the MacroGard® fed fish, which resulted in heightened tryptic enzyme activity. No effect on genes encoding antioxidative proteins was observed, whilst the immune response was clearly modulated by beta-glucan. At 11 dph complement component c3 was elevated whilst cytokines, antimicrobial peptides, toll like receptor 3 and heat shock protein 70 were not affected. At the later time point (24 dph) an anti-inflammatory effect in form of a down-regulation of hsp 70, tnf-alpha and il-1beta was observed. We conclude that the administration of beta-glucan induced an immunomodulatory response and could be used as an effective measure to increase survival in rearing of turbot.

Impact of mycophenolate mofetil loading on drug exposure in the early posttransplant period

Achieving adequate therapeutic levels of immunosuppressive medications is important in rejection prevention. This study examined exposure to mycophenolic acid (MPA) in kidney transplant patients within the first 5 days posttransplantation. Methods. This single-center, nonrandomized study of first solitary kidney allograft recipients receiving cyclosporine (n = 116) or tacrolimus (n = 50) included patients who received either 1 g or 1.5 g of mycophenolate mofetil twice daily starting postoperatively. Exposure to MPA was measured at days 3 and 5 posttransplant using published limited sampling time equations. Results. There were no significant differences in exposure in the cyclosporine-treated patients receiving 3-g (n = 22) compared to 2-g (n = 94) daily doses (AUC([0-12]) 33.8 +/- 10.0 mg*h/L versus 30.1 +/- 9.7 mg*h/L, P =.20, respectively). About half the patients in both groups had AUC([0-12]) < 30 mg*h/L on days 3 and 5 posttransplant. On the other hand, there was significantly greater exposure on day 3 in the tacrolimus-treated patients receiving 3 g (n = 21) compared to 2 g (n = 29) daily (AUC([0-12]) 43.1 +/- 9.0 mg*h/L versus 36.8 +/- 11.1 mg*h/L, P =.016, respectively). On day 3 one (4.8%) patient receiving 3 g had an AUC([0-12]) of < 30 mg*h/L; whereas, eight (27.5%) receiving 2 g were below this level (P =.068). The AUC([0-12]) levels were not different on day 5. Conclusions. Loading with higher doses of mycophenolate mofetil results in greater exposure and a trend toward more patients in the therapeutic window within the first week for tacrolimus- but not for cyclosporine-treated patients.

Do predators aggregate in response to pest density in agroecosystems? Assessing within-field spatial patterns

1. The spatial heterogeneity of predator populations is an important component of ecological theories pertaining to predator-prey dynamics. Most studies within agricultural fields show spatial correlation (positive or negative) between mean predator numbers and prey abundance across a whole field over time but generally ignore the within-field spatial dimension. We used explicit spatial mapping to determine if generalist predators aggregated within a soybean field, the size of these aggregations and if predator aggregation was associated with pest aggregation, plant damage and predation rate. 2. The study was conducted at Gatton in the Lockyer Valley, 90 km west of Brisbane, Australia. Intensive sampling grids were used to investigate within-field spatial patterns. The first row of each grid was located in a lucerne field (10 m from interface) and the remaining rows were in an adjacent soybean field. At each point on the grid the abundance of foliage-dwelling and ground-dwelling pests and predators was measured, predation rates [using sentinel Helicoverpa armigera (Hubner) egg cards] and plant damage were estimated. Eight grids were sampled across two summer cropping seasons (2000/01, 2001/02). 3. Predators exhibited strong spatial patterning with regions of high and low abundance and activity within what are considered to be uniform soybean fields. Ground-dwelling and foliage-dwelling predators were often aggregated in patches approximately 40 m across. 4. Lycosidae (wolf spiders) displayed aggregation and were consistently more abundant within the lucerne, with a decreasing trap catch with distance from the lucrene/soybean interface. This trend was consistent between subsequent grids in a single field and between fields. 5. The large amount of spatial variability in within-field arthropod abundance (pests and predators) and activity (egg predation and plant damage) indicates that whole field averages were misleading. This result has serious implications for sampling of arthropod abundance and pest management decision-making based on scouting data. 6. There was a great deal of temporal change in the significant spatial patterns observed within a field at each sampling time point during a single season. Predator and pest aggregations observed in these fields were generally not stable for the entire season. 7. Predator aggregation did not correlate consistently with pest aggregation, plant damage or predation rate. Spatial patterns in predator abundance were not associated consistently with any single parameter measured. The most consistent positive association was between foliage-dwelling predators and pests (significant in four of seven grids). Inferring associations between predators and prey based on an intensive one-off sampling grid is difficult, due to the temporal variability in the abundance of each group. 8. Synthesis and applications. This study demonstrated that generalist predator populations are rarely distributed randomly and field edges and adjacent crops can have an influence on within-field predator abundance. This must be considered when estimating arthropod (pest and predator) abundance from a set of samples taken at random locations within a field.

Induction of protein degradation in skeletal muscle by a phorbol ester involves upregulation of the ubiquitin-proteasome proteolytic pathway

Although muscle atrophy is common to a number of disease states there is incomplete knowledge of the cellular mechanisms involved. In this study murine myotubes were treated with the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) to evaluate the role of protein kinase C (PKC) as an upstream intermediate in protein degradation. TPA showed a parabolic dose-response curve for the induction of total protein degradation, with an optimal effect at a concentration of 25 nM, and an optimal incubation time of 3 h. Protein degradation was attenuated by co-incubation with the proteasome inhibitor lactacystin (5 μM), suggesting that it was mediated through the ubiquitin-proteasome proteolytic pathway. TPA induced an increased expression and activity of the ubiquitin-proteasome pathway, as evidenced by an increased functional activity, and increased expression of the 20S proteasome α-subunits, the 19S subunits MSS1 and p42, as well as the ubiquitin conjugating enzyme E214k, also with a maximal effect at a concentration of 25 nM and with a 3 h incubation time. There was also a reciprocal decrease in the cellular content of the myofibrillar protein myosin. TPA induced activation of PKC maximally at a concentration of 25 nM and this effect was attenuated by the PKC inhibitor calphostin C (300 nM), as was also total protein degradation. These results suggest that stimulation of PKC in muscle cells initiates protein degradation through the ubiquitin-proteasome pathway. TPA also induced degradation of the inhibitory protein, I-κBα, and increased nuclear accumulation of nuclear factor-κB (NF-κB) at the same time and concentrations as those inducing proteasome expression. In addition inhibition of NF-κB activation by resveratrol (30 μM) attenuated protein degradation induced by TPA. These results suggest that the induction of proteasome expression by TPA may involve the transcription factor NF-κB. © 2005 Elsevier Inc. All rights reserved.

Aproveitamento sustentável do bagaço de cana de açúcar para obtenção do acetato de celulose

The sustainable use of waste resulting from the agribusiness is currently the focus of research, especially the sugar cane bagasse (BCA), being the lignocellulosic waste produced in greater volume in the Brazilian agribusiness, where the residual biomass has been applied in production energy and bioproducts. In this paper, pulp was produced in high purity from the (BCA) by pulping soda / anthraquinone and subsequent conversion to cellulose acetate. Commercial cellulose Avicel was used for comparison. The obtained cellulose acetate was homogeneous acetylation reaction by modifying the variables, the reaction time in hours (8, 12, 16, 20 and 24) and temperature in ° C (25 and 50). FTIR spectra showed characteristic bands identical to cellulosic materials, demonstrating the efficiency of separation by pulping. The characterization of cellulose acetate was obtained and by infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG / DTG / DSC), scanning electron microscopy (SEM) and determining the degree of substitution (DS ) for the cellulose acetate to confirm the acetylation. The optimal reaction time for obtaining diacetates and triacetates, at both temperatures were 20 and 24 h. Cellulose acetate produced BCA presented GS between 2.57 and 2.7 at 25 ° C and 50 ° C GS obtained were 2.66 and 2.84, indicating the actual conversion of cellulose BCA of di- and triacetates. Comparative mode, commercial cellulose Avicel GS showed 2.78 and 2.76 at 25 ° C and 2.77 to 2.75 at 50 ° C. Data were collected in time of 20 h and 24 h, respectively. The best result was for the synthesis of cellulose acetate obtained from the BCA GS 2.84 to 50 ° C and 24 hours, being classified as cellulose triacetate, which showed superior result to that produced with the commercial ethyl cellulose Avicel, demonstrating converting potential of cellulose derived from a lignocellulosic residue (BCA), low cost, prospects of commercial use of cellulose acetate

Presenting SAPUSS: solving aerosol problem by using synergistic strategies in Barcelona, Spain

This paper presents the summary of the key objectives, instrumentation and logistic details, goals, and initial scientific findings of the European Marie Curie Action SAPUSS project carried out in the western Mediterranean Basin (WMB) during September-October in autumn 2010. The key SAPUSS objective is to deduce aerosol source characteristics and to understand the atmospheric processes responsible for their generations and transformations - both horizontally and vertically in the Mediterranean urban environment. In order to achieve so, the unique approach of SAPUSS is the concurrent measurements of aerosols with multiple techniques occurring simultaneously in six monitoring sites around the city of Barcelona (NE Spain): a main road traffic site, two urban background sites, a regional background site and two urban tower sites (150 m and 545 m above sea level, 150 m and 80 m above ground, respectively). SAPUSS allows us to advance our knowledge sensibly of the atmospheric chemistry and physics of the urban Mediterranean environment. This is well achieved only because of both the three dimensional spatial scale and the high sampling time resolution used. During SAPUSS different meteorological regimes were encountered, including warm Saharan, cold Atlantic, wet European and stagnant regional ones. The different meteorology of such regimes is herein described. Additionally, we report the trends of the parameters regulated by air quality purposes (both gaseous and aerosol mass concentrations); and we also compare the six monitoring sites. High levels of traffic-related gaseous pollutants were measured at the urban ground level monitoring sites, whereas layers of tropospheric ozone were recorded at tower levels. Particularly, tower level night-time average ozone concentrations (80 +/- 25 mu g m(-3)) were up to double compared to ground level ones. The examination of the vertical profiles clearly shows the predominant influence of NOx on ozone concentrations, and a source of ozone aloft. Analysis of the particulate matter (PM) mass concentrations shows an enhancement of coarse particles (PM2.5-10) at the urban ground level (+64 %, average 11.7 mu g m(-3)) but of fine ones (PM1) at urban tower level (+28 %, average 14.4 mu g m(-3)). These results show complex dynamics of the size-resolved PM mass at both horizontal and vertical levels of the study area. Preliminary modelling findings reveal an underestimation of the fine accumulation aerosols. In summary, this paper lays the foundation of SAPUSS, an integrated study of relevance to many other similar urban Mediterranean coastal environment sites.

Geological reference standards (JLK-1,JSD-1, JSD-2, JSD-3,JMS-1, JMS-2) measured by Itrax-XRF core scanner in different exposure times

X-ray fluorescence (XRF) core-scanning is a fast and nondestructive technique to assess elemental variations of unprocessed sediments. However, although the exposure time of XRF-scanning directly affects the scanning counts and total measurement time, only a few studies have considered the influence of exposure time during the scan. How to select an optimal exposure time to achieve reliable results and reduce the total measurement time is an important issue. To address this question, six geological reference materials from the Geological Survey of Japan (JLK-1, JMS-1, JMS-2, JSD-1, JSD-2, and JSD-3) were scanned by the Itrax-XRF core scanner using the Mo- and the Cr-tube with different exposure times to allow a comparison of scanning counts with absolute concentrations. The regression lines and correlation coefficients of elements that are generally used in paleoenvironmental studies were examined for the different exposure times and X-ray tubes. The results show that for those elements with relatively high concentrations or high detectability, the correlation coefficients are higher than 0.90 for all exposure times. In contrast, for the low detectability or low concentration elements, the correlation coefficients are relatively low, and improve little with increased exposure time. Therefore, we suggest that the influence of different exposure times is insignificant for the accuracy of the measurements. Thus, caution must be taken when interpreting the results of elements with low detectability, even when the exposure times are long and scanning counts are reasonably high.

Particle characterization at CVAO during the 2007 RHaMBLe intensive

The chemical characterization of filter high volume (HV) and Berner impactor (BI) samples PM during RHaMBLe (Reactive Halogens in the Marine Boundary Layer) 2007 shows that the Cape Verde aerosol particles are mainly composed of sea salt, mineral dust and associated water. Minor components are nss-salts, OC and EC. The influence from the African continent on the aerosol constitution was generally small but air masses which came from south-western Europe crossing the Canary Islands transported dust to the sampling site together with other loadings. The mean mass concentration was determined for PM10 to 17 µg/m**3 from impactor samples and to 24.2 µg/m**3 from HV filter samples. Non sea salt (nss) components of PM were found in the submicron fractions and nitrate in the coarse mode fraction. Bromide was found in all samples with much depleted concentrations in the range 1-8 ng/m**3 compared to fresh sea salt aerosol indicating intense atmospheric halogen chemistry. Loss of bromide by ozone reaction during long sampling time is supposed and resulted totally in 82±12% in coarse mode impactor samples and in filter samples in 88±6% bromide deficits. A chloride deficit was determined to 8% and 1% for the coarse mode particles (3.5-10 µm; 1.2-3.5 µm) and to 21% for filter samples. During 14 May with high mineral dust loads also the maximum of OC (1.71 µg/m**3) and EC (1.25 µg/m**3) was measured. The minimum of TC (0.25 µg/m**3) was detected during the period 25 to 27 May when pure marine air masses arrived. The concentrations of carbonaceous material decrease with increasing particle size from 60% for the ultra fine particles to 2.5% in coarse mode PM. Total iron (dust vs. non-dust: 0.53 vs. 0.06 µg/m**3), calcium (0.22 vs. 0.03 µg/m**3) and potassium (0.33 vs. 0.02 µg/m**3) were found as good indicators for dust periods because of their heavily increased concentration in the 1.2 to 3.5 µm fraction as compared to their concentration during the non-dust periods. For the organic constituents, oxalate (78-151 ng/m**3) and methanesulfonic acid (MSA, 25-100 ng/m**3) are the major compounds identified. A good correlation between nss-sulphate and MSA was found for the majority of days indicating active DMS chemistry and low anthropogenic influences.

Aditivos químicos ou biológicos na ensilagem de cana-de-açúcar: 2. parâmetros ruminais e degradabilidade da matéria seca e das frações fibrosas

Objetivou-se avaliar o efeito da inclusão de aditivos na ensilagem de cana-de-açúcar (Saccharum officinarum L.) sobre a degradação de MS e de componentes da parede celular e sobre os parâmetros de fermentação ruminal em bovinos alimentados com dietas contendo essas silagens. Utilizaram-se cinco novilhos da raça Nelore providos de cânula ruminal, alocados em delineamento quadrado latino 5 ´ 5 e alimentados com dietas com 65% de volumoso (%) MS. Foram avaliadas cinco silagens (base úmida): controle - cana-de-açúcar, sem aditivos; uréia - cana-de-açúcar + 0,5% ureia; benzoato - cana-de-açúcar + 0,1% de benzoato de sódio; LP - cana-de-açúcar inoculada com Lactobacillus plantarum (1 ´ 10(6) ufc/g MV); LB - cana-de-açúcar inoculada com L. buchneri (3,6 ´ 10(5) ufc/g forragem). A forragem foi armazenada em silos do tipo poço por 90 dias antes do fornecimento aos animais. Os parâmetros ruminais foram afetados de forma moderada pelas silagens e tiveram forte efeito do horário de coleta de amostras. As concentrações molares médias dos ácidos acético, propiônico e butírico foram de 60,9; 19,3 e 10,2 mM, respectivamente. O ambiente ruminal proporcionado por dietas formuladas com silagens de cana-de-açúcar foi satisfatório e similar ao tradicionalmente observado em dietas contendo cana. O uso de aditivos na ensilagem influenciou, de forma não-significativa, a degradabilidade ruminal da MS e da MO, mas não alterou a degradabilidade ruminal da fração fibrosa. Os aditivos aplicados à cana-de-açúcar resultaram em pequenas alterações na maior parte das variáveis avaliadas. Apesar de a degradabilidade ruminal das silagens ter sido pouco afetada pelo uso de aditivos, os valores observados foram próximos aos observados para a cana-de-açúcar in natura.

In vitro study of interaction between quinine and Garcinia kola

Purpose: To investigate the interaction between quinine and Garcinia kola using an in vitro adsorption study. Methods: In vitro interaction between quinine and G. kola was conducted at 37 ± 0.1 °C. Adsorption of quinine (2.5 - 40 μg/ml) to 2.5 % w/v G. kola suspension was studied. Thereafter, quinine desorption process was investigated. The amount of quinine adsorbed and desorbed was quantified using HPLC. A Freundlich isotherm was constructed to describe the resulting data and percentage of quinine desorbed was determined from the desorption data. Results: An adsorption isotherm of the data gave a Freundlich constant (K) of 52.66 μg/g, with a slope of 0.69 indicating a high capacity and affinity of G. kola to adsorb quinine at a concentration smaller than 2.41 μg/g of G. kola. However the adsorptive capacity of G. kola for quinine at 37 ± 0.1 °C appears to be a saturable process as observed from the isotherm. Quinine desorption from G. kola peaked at 1 hour (37.51 %) and decreased to a constant amount (about 35 %) over the remaining sampling time. Conclusion: Quinine is adsorbed on G. kola in vitro. This suggests that concurrent administration of quinine and G. kola should be avoided, to prevent potential drug interaction and decreased drug bioavailability.

Fast Detection and Chemical Characterization of Gunshot Residues by CMV-GC-MS and LIBS

Gunshot residue (GSR) is the term used to describe the particles originating from different parts of the firearm and ammunition during the discharge. A fast and practical field tool to detect the presence of GSR can assist law enforcement in the accurate identification of subjects. A novel field sampling device is presented for the first time for the fast detection and quantitation of volatile organic compounds (VOCs). The capillary microextraction of volatiles (CMV) is a headspace sampling technique that provides fast results (< 2 min. sampling time) and is reported as a versatile and high-efficiency sampling tool. The CMV device can be coupled to a Gas Chromatography-Mass Spectrometry (GC-MS) instrument by installation of a thermal separation probe in the injection port of the GC. An analytical method using the CMV device was developed for the detection of 17 compounds commonly found in polluted environments. The acceptability of the CMV as a field sampling method for the detection of VOCs is demonstrated by following the criteria established by the Environmental Protection Agency (EPA) compendium method TO-17. The CMV device was used, for the first time, for the detection of VOCs on swabs from the hands of shooters, and non-shooters and spent cartridges from different types of ammunition (i.e., pistol, rifle, and shotgun). The proposed method consists in the headspace extraction of VOCs in smokeless powders present in the propellant of ammunition. The sensitivity of this method was demonstrated with method detection limits (MDLs) 4-26 ng for diphenylamine (DPA), nitroglycerine (NG), 2,4-dinitrotoluene (2,4-DNT), and ethyl centralite (EC). In addition, a fast method was developed for the detection of the inorganic components (i.e., Ba, Pb, and Sb) characteristic of GSR presence by Laser Induced Breakdown Spectroscopy (LIBS). Advantages of LIBS include fast analysis (~ 12 seconds per sample) and good sensitivity, with expected MDLs in the range of 0.1-20 ng for target elements. Statistical analysis of the results using both techniques was performed to determine any correlation between the variables analyzed. This work demonstrates that the information collected from the analysis of organic components has the potential to improve the detection of GSR.

Sintesi e caratterizzazione di materiali polimerici water-soluble per applicazioni nel campo del fotovoltaico organico

The need to use renewable energy sources, due to the massive production of pollution for the energy production, has led to the development of new technologies for the use of solar energy. The purpose of this thesis project is to synthesize and characterize new thiophene-based polymeric materials processable in water, a green solvent, for the construction of organic solar cells, promising and versatile devices used for the production of electric energy. For this, a highly regioregular polymer was synthesized through GRIM polymerization (Grignard Metathesis Polymerization) on which a study was performed to identify the optimal reaction time.

Distributed non-cooperative robust economic predictive control for dynamically coupled linear systems.

In this thesis, a tube-based Distributed Economic Predictive Control (DEPC) scheme is presented for a group of dynamically coupled linear subsystems. These subsystems are components of a large scale system and control inputs are computed based on optimizing a local economic objective. Each subsystem is interacting with its neighbors by sending its future reference trajectory, at each sampling time. It solves a local optimization problem in parallel, based on the received future reference trajectories of the other subsystems. To ensure recursive feasibility and a performance bound, each subsystem is constrained to not deviate too much from its communicated reference trajectory. This difference between the plan trajectory and the communicated one is interpreted as a disturbance on the local level. Then, to ensure the satisfaction of both state and input constraints, they are tightened by considering explicitly the effect of these local disturbances. The proposed approach averages over all possible disturbances, handles tightened state and input constraints, while satisfies the compatibility constraints to guarantee that the actual trajectory lies within a certain bound in the neighborhood of the reference one. Each subsystem is optimizing a local arbitrary economic objective function in parallel while considering a local terminal constraint to guarantee recursive feasibility. In this framework, economic performance guarantees for a tube-based distributed predictive control (DPC) scheme are developed rigorously. It is presented that the closed-loop nominal subsystem has a robust average performance bound locally which is no worse than that of a local robust steady state. Since a robust algorithm is applying on the states of the real (with disturbances) subsystems, this bound can be interpreted as an average performance result for the real closed-loop system. To this end, we present our outcomes on local and global performance, illustrated by a numerical example.