Using the MixAlco process, biomass can be converted into carboxylic acids, which can be chemically converted into mixed alcohol
fuels. This study focused on the use of countercurrent fermentation to anaerobically convert sugarcane bagasse and chicken
manure to mixed carboxylic acids using a mixed culture of mesophilic microorganisms from terrestrial and marine sources. Bagasse
was pretreated with lime to increase digestibility. The continuum particle distribution model (CPDM) simulated continuous
fermentors based on data collected from batch experiments. This model saves considerable time in determining optimum operating
conditions. For an 80% bagasse/20% chicken manure fermentation with terrestrial inoculum at a volatile solids loading rate
(VSLR) of 7.36 g/(L of liquid·d) and a liquid residence time (LRT) of 8.88 d, total carboxylic acid productivity, total acid
selectivity, and yield were 2.49 g/(L of liquid·d), 0.581 g of total acid/g of VS digested, and 0.338 g of total acid/g of
VS fed, respectively, at a concentration of 18.7 g of total acid/L. At the same VSLR and LRT, fermentation with marine inoculum
gave higher total acid productivity, total acid selectivity, and yield than fermentation with terrestrial inoculum. For an
80% bagasse/20% chicken manure fermentation with marine inoculum at a VSLR of 3.83 g/(L of liquid·d) and an LRT of 12.1 d,
total carboxylic acid productivity, total acid selectivity, and yield were 1.38 g/(L of liquid·d), 0.667 g of total acid/g
of VS digested, and 0.359 g of total acid/g of VS fed, respectively, at a concentration of 16.2 g of total acid/L. 相似文献
Efforts to discover new drugs for Alzheimer's disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including β-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Aβ???? induced neuronal cell death at 1 μM were significantly greater than those of the potent single target compound, BACE1 inhibitor IV and were comparable to curcumin. The observed synergistic effect resulting from the reduction of the Aβ???? neurotoxicity cascade substantiates the validity of our multifunctional strategy in drug discovery for Alzheimer's disease. 相似文献
Nevirapine (NVP) and its structurally related analogs including nicotinamide (NAM), benzamide (BZM) and benzophenone (BZP) were used as templates in the synthesis of molecularly imprinted polymers for NVP. Molecular modeling was used to estimate binding energy of the complex formation between methacrylic acid (MAA) monomer and the selected templates, while equilibrium binding studies were applied to evaluate the polymer binding efficiency. The data indicated that NAM is the best candidate to prepare MIPs for retaining NVP due to a relatively similar binding energy between the NVP–MAA and NAM–MAA complex. The NAM-imprinted polymer showed a high binding affinity and selectivity toward NVP. When the polymer was applied as a sorbent in solid-phase extraction of NVP from human plasma, high recovery and reproducibility were obtained.
Asphaltenes have been fractionated by liquid/liquid extraction, yielding four subfractions. The characteristics of fractionated asphaltenes were studied with respect to solubility, aromaticity, heteroatom content, and diffusion behavior. It was observed that asphaltenes from the four subfractions showed variations in their tendency to flocculate and also distinct differences in aromaticity. Furthermore, NMR self-diffusion studies showed that the average diffusion coefficients varied for asphaltenes from the different subfractions. The results suggest a variation in average size and stability between asphaltenes, depending on what subfraction they belong to. The subfraction that consisted of asphaltenes with the largest average size and the highest aromaticity was also found to contain the asphaltenes that had the strongest tendency to flocculate. 相似文献
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play key roles in promoting cell survival and proliferation through the phosphorylation of various substrates. Remarkable antitumour activity is found in many inhibitors that act upstream of the ERK pathway. However, drug-resistant tumour cells invariably emerge after their use due to the reactivation of ERK1/2 signalling. ERK1/2 inhibitors have shown clinical efficacy as a therapeutic strategy for the treatment of tumours with mitogen-activated protein kinase (MAPK) upstream target mutations. These inhibitors may be used as a possible strategy to overcome acquired resistance to MAPK inhibitors. Here, we report a class of repeat proteins—designed ankyrin repeat protein (DARPin) macromolecules targeting ERK2 as inhibitors. The structural basis of ERK2–DARPin interactions based on molecular dynamics (MD) simulations was studied. The information was then used to predict stabilizing mutations employing a web-based algorithm, MAESTRO. To evaluate whether these design strategies were successfully deployed, we performed all-atom, explicit-solvent molecular dynamics (MD) simulations. Two mutations, Ala → Asp and Ser → Leu, were found to perform better than the original sequence (DARPin E40) based on the associated energy and key residues involved in protein-protein interaction. MD simulations and analysis of the data obtained on these mutations supported our predictions. 相似文献
The total and partial solubility parameters (dispersion, polar and hydrogen‐bonding solubility parameters) of ten ionic liquids were determined. Intrinsic viscosity approaches were used that encompassed a one‐dimensional method (1D‐Method), and two different three‐dimensional methods (3D‐Method1 and 3D‐Method2). The effect of solvent type, the dimethylacetamide (DMA) fraction in the ionic liquid, and dissolution temperature on solubility parameters were also investigated. For all types of effect, both the 1D‐Method and 3D‐Method2 present the same trend in the total solubility parameter. The partial solubility parameters are influenced by the cation and anion of the ionic liquid. Considering the effect on partial solubility parameters of the solvent type in the ionic liquid, it was observed that in both 3D methods, the dispersion and polar parameters of a 1‐ethyl‐3‐methylimidazolium acetate/solvent (60:40 vol %) mixture tend to increase as the total solubility parameter of the solvent increases. 相似文献
Nevirapine (NVP) and its structurally related analogs including nicotinamide (NAM), benzamide (BZM) and benzophenone (BZP) were used as templates in the synthesis of molecularly imprinted polymers for NVP. Molecular modeling was used to estimate binding energy of the complex formation between methacrylic acid (MAA) monomer and the selected templates, while equilibrium binding studies were applied to evaluate the polymer binding efficiency. The data indicated that NAM is the best candidate to prepare MIPs for retaining NVP due to a relatively similar binding energy between the NVP–MAA and NAM–MAA complex. The NAM-imprinted polymer showed a high binding affinity and selectivity toward NVP. When the polymer was applied as a sorbent in solid-phase extraction of NVP from human plasma, high recovery and reproducibility were obtained. 相似文献
The reaction mechanism of creatinine-creatininase binding to form creatine as a final product has been investigated by using
a combined ab initio quantum mechanical/molecular mechanical approach and classical molecular dynamics (MD) simulations. In
MD simulations, an X-ray crystal structure of the creatininase/creatinine was modified for creatininase/creatinine complexes
and the MD simulations were run for free creatininase and creatinine in water. MD results reveal that two X-ray water molecules
can be retained in the active site as catalytic water. The binding free energy from Molecular Mechanics Poisson-Boltzmann
Surface Area calculation predicted the strong binding of creatinine with Zn2+, Asp45 and Glu183. Two step mechanisms via Mn2+/Zn2+ (as in X-ray structure) and Zn2+/Zn2+ were proposed for water adding step and ring opening step with two catalytic waters. The pathway using synchronous transit
methods with local density approximations with PWC functional for the fragment in the active region were obtained. Preferable
pathway Zn2+/Zn2+ was observed due to lower activation energy in water adding step. The calculated energy in the second step for both systems
were comparable with the barrier of 26.03 and 24.44 kcal/mol for Mn2+/Zn2+ and Zn2+/Zn2+, respectively. 相似文献
Exon 2 of the Bcl-x gene undergoes alternative splicing in which the Bcl-xS splice variant promotes apoptosis in contrast to the anti-apoptotic splice variant Bcl-xL. In this study, the regulation of the alternative splicing of pre-mRNA of Bcl-x was examined in response to emetine. Treatment of different types of cancer cells with emetine dihydrochloride downregulated the level of Bcl-xL mRNA with a concomitant increase in the mRNA level of Bcl-xS in a dose- and time-dependent manner. Pretreatment with calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), blocked emetine-induced alternative splicing in contrast to okadaic acid, a specific inhibitor of PP2A in cells, demonstrating a PP1-mediated mechanism. Our finding on the regulation of RNA splicing of members of the Bcl-2 family in response to emetine presents a potential target for cancer treatment. 相似文献