發作性血色素尿症ニ就テ

The α4β2 nicotinic acetylcholine receptor (nAChR) is the most abundant subtype in the brain and exists in two functional stoichiometries: (α4)3(β2)2 and (α4)2(β2)3. A distinct feature of the (α4)3(β2)2 receptor is the biphasic activation response to the endogenous agonist acetylcholine, where it is activated with high potency and low efficacy when two α4-β2 binding sites are occupied and with low potency/high efficacy when a third α4-α4 binding site is occupied. Further, exogenous ligands can bind to the third α4-α4 binding site and potentiate the activation of the receptor by ACh that is bound at the two α4-β2 sites. We propose that perturbations of the recently described pre-activation step when a third binding site is occupied are a key driver of these distinct activation properties. To investigate this, we used a combination of simple linear kinetic models and voltage clamp electrophysiology to determine whether transitions into the pre-activated state were increased when three binding sites were occupied. We separated the binding at the two different sites with ligands selective for the α4-β2 site (Sazetidine-A and TC-2559) and the α4-α4 site (NS9283) and identified that when a third binding site was occupied, changes in the concentration-response curves were best explained by an increase in transitions into a pre-activated state. We propose that perturbations of transitions into a pre-activated state are essential to explain the activation properties of the (α4)3(β2)2 receptor by acetylcholine and other ligands. Considering the widespread clinical use of benzodiazepines, this discovery of a conserved mechanism that benzodiazepines and ACh potentiate receptor activation via a third binding site can be exploited to develop therapeutics with similar properties at other cys-loop receptors

On the independence of hydrogen production from methanogenic suppressor in olive mill wastewater

Anaerobic degradation of olive mill wastewater (OMW) at concentrations ranging from 2 to 100 g/L of chemical oxygen demand (COD) was assessed in batch assays. Methane was the main final product obtained for the lower concentrations tested. For 25 g COD/L, H2 was temporarily produced, albeit H2 depletion occurred, likely due to homoacetogenesis, since acetate was formed concomitantly. Hydrogen was produced and accumulated permanently in the assays containing 50 g COD/L of OMW. Methanogenesis and homoacetogenesis were naturally inhibited, suggesting that hydrogen recovery from OMW can be performed without the addition of methanogenic suppressors such as 2-bromoethanosulfonate. This fact opens new perspectives for the utilization of high OMW concentrations in a two-stage valorisation process combining biohydrogen and biomethane production.The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013, the FCT Project RECI/BBB-EBI/0179/2012, the Project "BioEnv - Biotechnology and Bioengineering for a sustainable world", REF. NORTE-07-0124-FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER. Also through the project PTDC/ENR/69755/2006 and grants given to Marta Goncalves SFRH/BD/40746/2007, Jose Carlos Costa SFRH/BDP/48962/2008 and Angela A Abreu SFRH/BPD/82000/2011

Combining Ecohydrological Catchment Modeling and Water Quality Monitoring Data to Assess Nitrogen Pollution in the Swist River Basin, Germany

Legislation like the EU Water Framework Directive demands the development as well as implementation of catchment-scale monitoring and management plans to control pollution of surface waters and ensure their good status. Water pollution with excess amounts of reactive nitrogen (N) - for example nitrate - can cause environmental problems like eutrophication while also posing potential health risks to humans. Knowledge of pollution sources and their relative importance in a given catchment is a prerequisite for developing targeted monitoring strategies and efficient management plans. The process of quantifying the contribution of each pollution source to overall pollution in a catchment is called source apportionment. Due to the abundance of pollution sources as well as their heterogeneity in time and space, source apportionment solely based on water quality monitoring is not feasible in large catchments, especially with regard to non-point source (diffuse) pollution. Ecohydrological computer models can be used to complement water quality monitoring data in space and time, identify critical source areas and carry out source apportionment studies. The overall research aim of the present thesis is to assess N pollution of surface waters in the Swist river basin, Germany, from 2012 to 2018 using the ecohydrological catchment model SWAT (Soil and Water Assessment Tool). Calibration of SWAT using Monte Carlo analysis generated a SWAT model ensemble allowing for analysis of modeling uncertainty. Furthermore, two independent reference data sets on diffuse N pollution in the Swist basin were available for comparison with the SWAT simulation results: (1) An emission inventory from upscaled edge-of-field monitoring data and (2) raster data generated by the AGRUM modeling system. The calibrated SWAT models predicted a mean diffuse N emission load of 8.1 kg/(ha a) for the entire Swist catchment area in the study period (median: 6.9 kg/(ha a)). Agricultural tile drainage was identified as the most important emission pathway in the catchment, shaping much of the spatial variability in diffuse N pollution. In contrast, due to missing groundwater contact in large parts of the catchment (a consequence of lignite mining north of the study area), surface waters received only minimal N from groundwater, possibly indicating a dominance of faster (tile drains) over slower (groundwater) emission pathways in the catchment. The highest diffuse N loads were predicted near the headwaters of the Schiessbach tributary by all SWAT models, making this region a likely critical source area for N in the catchment. On average, wastewater treatment plants contributed approximately one fourth (26.8 %) of overall N pollution in the simulations. As all these findings were basically consistent between the SWAT simulations and the two reference data sets, they can be used with relative confidence in the future to focus monitoring efforts, devise emission control strategies and implement effective mitigation measures. However, comparison of the available data also revealed some meaningful discrepancies, highlighting the remaining uncertainties in the results. Diffuse N emission loads simulated by the SWAT ensemble ranged from 4.7 to 11.4 kg/(ha a) (excluding one outlier at 15.9 kg/(ha a)). Since the two reference data sets mostly agree with SWAT in the order of magnitude of these values, the results are considered a realistic appraisal of diffuse N pollution in the Swist catchment. Still, with a factor of more than two (or three when including the outlier) between the upper and lower end of the uncertainty interval, the exact amount of N released to the Swist and its tributaries remains difficult to quantify. Although the general ranking of the individual pathways is mostly stable between the SWAT models and likewise confirmed by the reference data, the relative uncertainty intervals associated with their N contributions are even wider than for the overall emission loads. Apart from the Schiessbach headwaters, no other obvious critical source area candidate emerged among the SWAT simulation results and the reference data, with regions of high N emission loads mostly fluctuating between the different model results. The simulated contributions from wastewater treatment plants ranged from 14.7 to 36.7 % of overall N emissions in the catchment. For a future continuation of SWAT modeling in the Swist catchment to assess N pollution, there are several possibilities to potentially reduce the uncertainty in the simulation results. First, including additional data and/or objective functions in model calibration probably helps to better constrain the SWAT parameters. Second, the correction of some deficiencies in the model setup (i.e. input data and model structure) - for example in the amounts of applied N fertilizer or the omission of combined sewer overflows - makes model calibration presumably more efficient and may eliminate potential bias in the simulation results. In summary, ecohydrological catchment modeling with SWAT in the present thesis was successful in generating novel insights regarding N pollution in the Swist catchment. Here, model-based source apportionment benefited immensely from the extraordinary wealth of monitoring data available for the Swist catchment and the possibility to compare the SWAT modeling results to two independent reference data sets for the study area. This underscores the importance of comprehensive monitoring and knowledge of relevant local conditions to reach a sound understanding of surface water pollution on the catchment scale

Ethanol production from Sorghum bicolor using both separate and simultaneous saccharification and fermentation in batch and fed batch systems

The objective of this work was to find the best combination of different experimental conditions during pre-treatment, enzymatic saccharification, detoxification of inhibitors and fermentation of Sorghum bicolor straw for ethanol production. The optimization of pre-treatment using different concentrations of dilute sulfuric acid, various temperatures and residence times was achieved at 121°C, 1% acid concentration, 60 min residence time and enzyme saccharification using cellulase (celluclast 1.5 L) and -glucosidase (Novozyme 188) at 50°C and pH 4.8 for 48 h. Different surfactants were used in order toincrease the monomeric sugar during enzymatic hydrolysis and it has been observed that the addition of these surfactants contributed significantly in cellulosic conversion but no effect was shown onhemicellulosic hydrolysis. Fermentability of hydrolyzate was tested using Saccharomyces cerevisiae Ethanol RedTM and it was observed that simultaneous saccharification and fermentation (SSF) with bothbatch and fed batch resulted in better ethanol yield as compared to separate hydrolysis and fermentation (SHF). Detoxification of furan during SHF facilitated reduction in fermentation time from 96to 48 h. 98.5% theoretical yield was achieved in SHF with detoxification experiment attaining an ethanol concentration and yield of 23.01 gL-1 and 0.115 gg-1 DM respectively. During the SSF batch and fed batch fermentation, the maximum yields of ethanol per gram of dry matter were 0.1257 and 0.1332 g respectively

Analysis of vadose zone inhomogeneity toward distinguishing recharge rates: Solving the nonlinear interface problem with Newton method

Citation: Steward, D. R. (2016). Analysis of vadose zone inhomogeneity toward distinguishing recharge rates: Solving the nonlinear interface problem with Newton method. Water Resources Research, 52(11), 8756-8774. doi:10.1002/2016wr019222Recharge from surface to groundwater is an important component of the hydrological cycle, yet its rate is difficult to quantify. Percolation through two-dimensional circular inhomogeneities in the vadose zone is studied where one soil type is embedded within a uniform background, and nonlinear interface conditions in the quasilinear formulation are solved using Newton's method with the Analytic Element Method. This numerical laboratory identifies detectable variations in pathline and pressure head distributions that manifest due to a shift in recharge rate through in a heterogeneous media. Pathlines either diverge about or converge through coarser and finer grained materials with inverse patterns forming across lower and upper elevations; however, pathline geometry is not significantly altered by recharge. Analysis of pressure head in lower regions near groundwater identifies a new phenomenon: its distribution is not significantly impacted by an inhomogeneity soil type, nor by its placement nor by recharge rate. Another revelation is that pressure head for coarser grained inhomogeneities in upper regions is completely controlled by geometry and conductivity contrasts; a shift in recharge generates a difference Dp that becomes an additive constant with the same value throughout this region. In contrast, shifts in recharge for finer grained inhomogeneities reveal patterns with abrupt variations across their interfaces. Consequently, measurements aimed at detecting shifts in recharge in a heterogeneous vadose zone by deciphering the corresponding patterns of change in pressure head should focus on finer grained inclusions well above a groundwater table