Predicted secondary structure and membrane topology of the scrapie prion protein

The integral membrane sialoglycoprotein PrP^Sc is the only identifiablecomponent of the scrapie prion. Scrapie in animals and Creutzfeldt-Jakobdisease in humans are transmissible, degenerative neurologicaldiseases caused by prions. Standard predictive strategies havebeen used to analyze the secondary structure of the prion proteinin conjunction with Fourier analysis of the primary sequencehydrophobicities to detect potential amphipathic regions. Severalhydrophobic segments, a proline- and glycine-rich repeat regionand putative glycosylation sites are incorporated into a modelfor the integral membrane topology of PrP. The complete aminoacid sequences of the hamster, human and mouse prion proteinsare compared and the effects of residue substitutions upon thepredicted conformation of the polypeptide chain are discussed.While PrP has a unique primary structure, its predicted secondarystructure shares some interesting features with the serum amyloidA proteins. These proteins undergo a post-translational modificationto yield amyloid A, molecules that share with PrP the abilityto polymerize into birefringent filaments. Our analyses mayexplain some experimental observations on PrP, and suggest furtherstudies on the properties of the scrapie and cellular PrP isoforms.     

Mathematical modelling and simulation of a recycle dialysis membrane reactor in a reversed micellar system

A mathematical framework was developed for the evaluation of a recycle dialysis membrane reactor (RDMR). The lipase-catalyzed hydrolysis of olive oil in an AOT-iso-octane reversed micellar system was employed as a model. Three specific operational strategies have been considered, namely batch, fed-batch, and fed-batch-bleed. Simulation shows the conversion of substrate to be strongly dependent on efficient use of the substrate, since the permeability coefficients of both substrate and product are quite similar. Sensitivity analyses were performed to assess the influences of various parameters (membrane area, substrate feed rate, solvent bleed rate and permeability) on the performance of the reactor in different modes of operation. The analyses presented are useful to assist the optimization of the operational strategy used for the RDMR system.     

Separation of di- and tripeptides with solvent extraction and an emulsion liquid membrane

The extraction equilibria of various di- and tripeptides with di-2-ethylhexylphosphoric acid (D2EHPA) were studied at low pH values. The complex extracted to organic phase consisted of one molecule of peptide and two molecules of D2EHPA dimer. The extraction constants of the peptides correlated well with the distribution coefficients of peptides between 1-octanol and water, which is a measure of hydrophobicity. The permeation rates of peptides through an emulsion liquid membrane were examined by using D2EHPA as a carrier, Span 80 as an emulsifier and kerosene as a diluent. The rates varied considerably with peptide type, depending upon the hydrophobicity.     

Evidence for a role of the membrane-proximal region of herpes simplex virus type 1 glycoprotein H in membrane fusion and virus inhibition

We have identified a putative membrane-interacting domain preceding the transmembrane domain of the Herpes simplex virus type 1 (HSV-1) glycoprotein H (gH). Peptides derived from this region interact strongly with membranes and show a high tendency to partition at the interface. This region is predicted to bind at the membrane interface by adopting an alpha helical structure. Peptides representing either the HSV-1 gH pretransmembrane region or a scrambled control with a different hydrophobic profile at the point of interface have been studied. The peptides derived from this domain of gH induce the fusion of liposomal membranes, adopt helical conformations in membrane mimetic environments and are able to inhibit HSV-1 infectivity. The pretransmembrane region appears to be a common feature in viral fusion proteins of several virus families, and such a feature might be related to their fusogenic function. The identification of membrane-interacting regions capable of modifying the biophysical properties of phospholipid membranes lends weight to the view that such domains might function directly in the fusion process and could facilitate the future development of HSV-1 entry inhibitors.     

Pervaporative permeations of homologous series of alcohol aqueous mixtures through a hydrophilic membrane

The permeation behaviors of permeants were investigated in the pervaporation of a homologous series of alcohol aqueous mixtures through a hydrophilic poly(vinyl alcohol) (PVA). The PVA membrane was crosslinked with glutaraldehyde. A homologous series of alcohols used in this study were methanol, ethanol, 1‐propanol, and 1‐butanol. The pervaporation experiments were carried out with feed having 70–97 wt % of alcohol contents and at various feed temperatures. In a high alcohol content above 92 wt %, the permeation rate was increased in the order of the interaction strength between alcohol and water in the feed. However, in a low alcohol content below 90 wt %, the tendency of the permeation rate was found to be the opposite, indicating that the interactions between permeant constituents play an important role in determining the permeation and separation of the mixtures. These observations were discussed in terms of changes in the interaction between the permeant/permeant or the permeant/membrane in varying feed compositions and feed temperatures. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 703–713, 2001     

Head-to-tail cyclization of a heptapeptide eliminates its cytotoxicity and significantly increases its inhibition effect on amyloid β-protein fibrillation and cytotoxicity

Amyloid-β (Aβ) protein aggregation is the main hallmark of Alzheimer’s disease (AD). Inhibition of Aβ fibrillation is thus a promising therapeutic approach to the prevention and treatment of AD. Recently, we designed a heptapeptide inhibitor, LVFFARK (LK7). LK7 shows a promising inhibitory capability on Aβ fibrillation, but is prone to self-assembling and displays high cytotoxicity, which would hinder its practical application. Herein, we modified LK7 by a head-to-tail cyclization and obtained a cyclic LK7 (cLK7). cLK7 exhibits a different self-assembly behavior from LK7, and has higher stability against proteolysis than LK7 and little cytotoxicity to SH-SY5Y cells. Thermodynamic analysis revealed that both LK7 and cLK7 could bind to Aβ₄₀ by electrostatic interactions, hydrogen bonding and hydrophobic interactions, but the binding affinity of cLK7 for Aβ₄₀ (K_D = 4.96 µmol/L) is six times higher than that of LK7 (K_D = 32.2 µmol/L). The strong binding enables cLK7 to stabilize the secondary structure of Aβ₄₀ and potently inhibit its nucleation, fibrillation and cytotoxicity at extensive concentration range, whereas LK7 could only moderately inhibit Aβ₄₀ fibrillation and cytotoxicity at low concentrations. The findings indicate that the peptide cyclization is a promising approach to enhance the performance of peptide-based amyloid inhibitors.     

Modelling nutrient transport in hollow fibre membrane bioreactor for growing bone tissue with consideration of multi-component interactions

Current work in bone tissue engineering (BTE) suggests that hollow fibre membrane bioreactors (HFMBs) can be used to grow artificial bone tissue which may then be implanted in humans to treat various bone defects. The HFMBs mimic the blood capillary networks in human bones and are able to maintain high concentrations of nutrients by minimising mass transfer distance. To further establish this method and to develop effective BTE protocols, nutrient transport behaviour in the HFMB must be characterised. By doing so, the quantitative relationships between the cell environments and, bioreactor operating conditions and designs can be elucidated. This also paves the way for possible improvement and optimisation of the HFMB performance. However, characterising the nutrients transport properties in HFMB are not straightforward as online measurements of key parameters are almost impossible at the moment. This is due to the very small size and the stringent operating conditions of the bioreactors. Hence, much work is needed on mathematical modelling of mass transport in these bioreactors. In this paper, we present a rigorous framework for modelling mass transport in HFMB for growing bone tissue. In particular, we consider the effects of hydrodynamics and multi-component interactions on nutrient transport profiles. The developed framework is then used to study the behaviour of nutrient transport in HFMB for bone tissue growth for various operating conditions with a view to generalise their effects as far as possible. Maxwell-Stefan, Navier-Stokes and reaction kinetic equations are combined to quantify the multi-component nutrient transport behaviour in the bioreactor. The framework also relies on the use of a single hollow fibre (Krogh cylinder assumption), which is representative of the whole fibre bundle. The numerical solutions of the governing model equations are obtained using finite element method. The effects of different bioreactor designs (e.g., fibre length, lumen thickness, etc.) and process parameters (e.g., nutrient inlet concentration, fluid velocity, etc.) on multi-component nutrient concentration profiles (e.g., glucose and oxygen) are simulated. The results show that the HFMB designs and process parameters may be optimised to further enhance mass transport for growing bone tissues.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

Theoretical analysis of inhibition effect on steady states of enzymatic membrane reactor with substrate and product retention for reaction producing weak acid

The aim of this study is to formulate a model of enzymatic membrane reactor (EMR), i.e., a continuous, stirred tank bioreactor with full enzyme recycle, for a reaction producing a weak acid, and to explore the effect of substrate and product inhibition of different mechanisms coupled with transport properties of the membrane on the static behaviour of the system. The inhibition of an enzyme by a substrate leads to the non-monotonicity of reaction rate expression with respect to the substrate concentration. If a product of enzymatic reaction, taking place in the EMR, influences the pH of a reaction mixture this is also the factor causing the non-monotonicity of the substrate and product dependent reaction rate. The character of these dependencies affects substantially the structure of the steady states of the reactor. The bifurcation diagrams, shown in the work, are of different characters depending on the bifurcation parameter. It has been found, that bifurcation diagrams for competitive and uncompetitive inhibition by a substrate differ in the number and position of bifurcation points. Steady states of multiplicity five have been localised in case of uncompetitive inhibition by the substrate at high affinity of the enzyme to this substrate. Retention of reagents, related to transport properties of a membrane, influences significantly the effectiveness of a process. A specially written software in Delphi™ has been used for the calculations.     

Theoretical and experimental analysis of methane steam reforming in a membrane reactor

Thermal effects on methane steam reforming process were analyzed, in a Pd-Ag (23wt%) membrane reactor as a function of several parameters, such as temperature, reactant and sweep-gas flow rate, and reactant molar ratio. Heat transfer from the oven was very important for the outlet methane conversion, which also depends on the temperature profile along the reactor. In particular, when the reactant flow rate was high the conversion degree decreased because the energy supplied was not sufficient to maintain the temperature in the reactor. A non-isothermal mathematical model was presented which reproduced the experimental data.     

Fabrication and characterization of a novel Nafion-PTFE composite hollow fiber membrane

Nafion has been widely used in electrochemistry, but there are only a few reports on its application in other fields, such as, gas separation, even though it exhibits good performance. The primary reason for that is the high cost of Nafion and making a composite membrane with a thin Nafion layer is a potential solution to solve this problem. In this study, a novel Nafion-PTFE composite hollow fiber membrane, which had a thin (~5 μm) and detect-free Nafion layer on PTFE surface, without Nafion filling substrate pores was developed, differing from the reported ones in which Nafion resin was required to impregnate into porous PTFE membrane as thorough as possible to ensure the ion conductivity and operation stability. The surface morphology, crystallite, solubility in ethanol/water mixture, and water uptake of membranes were systemically investigated. The gas permeance tests were also conducted. The permeances of different gasses of prepared composite membranes were significantly enhanced compared with the commercial membranes due to the decrease of Nafion thicknesses, while the selectivity remained the same, verifying the detect-free structure of Nafion layer on PTFE substrate. This study provided a good reference for the preparation and application of low-cost Nafion composite membranes.     

Preparation,characterization, and permeation property of a liquid crystal/PDMS membrane material

By introducing the ordered and flowing liquid crystalline groups into polymeric membranes, a novel liquid crystal/polydimethylsiloxane (LC/PDMS) membrane material is synthesized with PDMS containing vinyl group, polymethylhydrosiloxane and cholesteric LC as matrix materials. The chemical structure, LC behaviors and mechanical performance of the LC/PDMS crosslinked membranes are characterized by using FTIR, differential scanning calorimetry (DSC), and polarized light microscopy with a hot stage. Some factors on permeability and permselectivity for carbon dioxide and nitrogen gas are also examined. These results suggest that the membrane‐forming property and permeation properties of the crosslinked membranes are obviously enhanced due to the introduction of the LC groups into PDMS and crosslinking reaction in the preparation process. At pressure difference of 0.1 MPa and testing temperature of 40°C, the permeability coefficient for carbon dioxide and ideal separation factor for carbon dioxide and nitrogen are up to 4667 Barrer and 24.0, respectively. In addition, the incorporation of LC containing unsaturated linkage has the potential for further modification reactions such as grafting and crosslinking. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

低膜面流速下曝气对管式膜水力特性及膜污染影响

采用曝气强化管式膜超滤高岭土混合液,考察了低膜面流速下曝气对强化膜分离过程影响,探讨了曝气对膜面水力特征及膜污染过程影响,并对过滤介质影响及膜污染阻力构成进行了研究。结果表明,在低膜面流速下,通过向管式膜引入曝气使膜表面形成气液两相流,可实现膜通量稳定保持在15L/(m²·h)以上。不仅如此,曝气的引入使膜表面雷诺数由1800~2500增至3300~4500,显著增强了膜表面湍流程度,并且实现了低膜面流速下使膜污染指数控制在较低水平,节省了运行能耗。此外,曝气的引入主要减轻了膜表面滤饼污染,使膜过滤总阻力减小且对高岭土截留效率影响不大,但强烈的膜面传质使高岭土粒径有减小趋势,并且膜表面形成污染阻力以不可逆污染层为主,不利于膜污染长周期控制。     

Roles of sponge sizes and membrane types in a single stage sponge-submerged membrane bioreactor for improving nutrient removal from wastewater for reuse

Sponge not only can reduce membrane fouling by means of mechanical cleaning and maintain a balance of suspended-attached microorganisms in submerged membrane bioreactor (SMBR), but also can enhance dissolved organic matter and nutrient removal. This study investigated the performance of three different sizes of sponge (S_28-30/45R, S_28-30/60R and S_28-30/90R) associated with continuous aerated SMBR. A laboratory-scale single stage sponge-SMBR (SSMBR) showed high performance for removing dissolved organic matter (>96%) and PO₄-P (>98.8), while coarse sponges such as S_28-30/45R, S_28-30/60R could achieve more than 99% removal of NH₄-N. When three-size sponges (S_28-30/45R, S_28-30/60R and S_28-30/90R) were mixed at a ratio of 1:1:1 and in conjunction with two kinds of membranes (0.1 µm hollow fiber and 2 µm nonwoven), the SSMBR system has proved its generic merits of superior treated effluent quality and less membrane fouling. The NH₄-N and PO₄-P removal were found excellent, which were more than 99.8% and over 99% respectively. Molecular weight distribution also indicated that major fractions of organic matter could be successfully removed by SSMBR.     

某钢铁厂污水回用项目反渗透膜污染的分析和清洗

经过污堵物质的分析,采用了合适的复合药剂,利用成熟的膜清洗工艺流程对膜组件进行了清洗研究。     

The Natural Products Beauveriolide I and III: a New Class of β‐Amyloid‐Lowering Compounds

Attacking Alzheimer's by ACAT : The aggregation of β‐amyloid peptides, especially Aβ₄₂, into senile plaques is a hallmark of Alzheimer's disease (AD). We show that the fungal natural products beauveriolides I and III can potently decrease Aβ secretion from cells expressing human amyloid precursor protein; this offers a potential new scaffold for the development of compounds with proven bioavailability for the treatment of AD.

     

Phase separation phenomena in solutions of polysulfone in mixtures of a solvent and a nonsolvent: relationship with membrane formation

The phase separation phenomena in ternary solutions of polysulfone (PSf) in mixtures of a solvent and a nonsolvent (N,N-dimethylacetamide (DMAc) and water, in most cases) are investigated. The liquid-liquid demixing gap is determined and it is shown that its location in the ternary phase diagram is mainly determined by the PSf-nonsolvent interaction parameter. The critical point in the PSf/DMAc/water system lies at a high polymer concentration of about 8% by weight. Calorimetric measurements with very concentrated PSf/DMAc/water solutions (prepared through liquid-liquid demixing, polymer concentration of the polymer-rich phase up to 60%) showed no heat effects in the temperature range of ?20°C to 50°C. It is suggested that gelation in PSf systems is completely amorphous. The results are incorporated into a discussion of the formation of polysulfone membranes.     

Hydrogen production from urea wastewater using a combination of urea thermal hydrolyser-desorber loop and a hydrogen-permselective membrane reactor

This work presents novel application of palladium-based membrane in a wastewater treatment loop of urea plant for hydrogen production. Urea wastewater treatment loop is based on combined thermal hydrolysis-desorption operations. The wastewater of urea plant includes ammonia and urea which in the current treatment loop; urea decomposes to ammonia and carbon dioxide. The catalytic hydrogen-permselective membrane reactor is proposed for hydrogen production from desorbed ammonia of urea wastewater which much of it discharges to air and causes environmental pollution. Therefore hydrogen is produced from decomposition of ammonia on nickel-alumina catalyst bed simultaneously and permeates from reaction side to shell side through thin layer of palladium-silver membrane. Also a sweep gas is used in the shell side for increasing driving force. In this way, 4588 tons/yr hydrogen is produced and environmental problem of urea plant is solved. The membrane reactor and urea wastewater treatment loop are modeled mathematically and the predicted data of the model are consistent with the experimental and plant data that show validity of the model. Also the effects of key parameters on the performance of catalytic hydrogen-permselective membrane reactor such as the temperature, pressure, thickness of Pd-Ag layer, configuration of flow and sweep gas flow ratio were examined.