New catanionic surfactants based on 1-alkyl-3-methylimidazolium alkylsulfonates, [C(n)H(2n+1)mim][CmH2m+1SO3]: mesomorphism and aggregation

Anionic and cationic alkyl-chain effects on the self-aggregation of both neat and aqueous solutions of 1-alkyl-3-methylimidazolium alkylsulfonate salts ([C(n)H(2n+ 1)mim][CmH2m+1SO3]; n = 8, 10 or 12; m = 1 and n = 4 or 8; m = 4 or 8) have been investigated. Some of these salts constitute a novel family of pure catanionic surfactants in aqueous solution. Examples of this class of materials are rare; they are distinct from both mixed cationic-anionic surfactants (obtained by mixing two salts) and gemini surfactants (with two or more amphiphilic groups bound by a covalent linker). Fluorescence spectroscopy and interfacial tension measurements have been used to determine critical micelle concentrations (CMCs), surface activity, and to compare the effects of the alkyl-substitution patterns in both the cation and anion on the surfactant properties of these salts. With relatively small methylsulfonate anions (n = 8, 10 and 12, m = 1), the salts behave as conventional single chain cationic surfactants, showing a decrease of the CMC upon increase of the alkyl chain length (n) in the cation. When the amphiphilic character is present in both the cation and anion (n = 4 and 8, m = 4 and 8), novel catanionic surfactants with CMC values lower than those of the corresponding cationic analogues, and which exhibited an unanticipated enhanced reduction of surface tension, were obtained. In addition, the thermotropic phase behaviour of [C(8)H(18)mim][C8H18SO3] (n = m = 8) was investigated using variable temperature X-ray scattering, polarising optical microscopy and differential scanning calorimetry; formation of a smectic liquid crystalline phase with a broad temperature range was observed.

Domestic fridge-freezer load aggregation to support ancillary services

Grid operators and electricity retailers in Ireland manage peak demand, power system balancing and grid congestion by offering relevant incentives to consumers to reduce or shift their load. The need for active consumers in the home using smart appliances has never been greater, due to increased variable renewable generation and grid constraints. In this paper an aggregated model of a single compressor fridge-freezer population is developed. A price control strategy is examined to quantify and value demand response savings during a representative winter and summer week for Ireland in 2020. The results show an average reduction in fridge-freezer operating cost of 8.2% during winter and significantly lower during summer in Ireland. A peak reduction of at least 68% of the average winter refrigeration load is achieved consistently during the week analysed using a staggering control mode. An analysis of the current ancillary service payments confirms that these are insufficient to ensure widespread uptake by the small consumer, and new mechanisms need to be developed to make becoming an active consumer attractive. Demand response is proposed as a new ancillary service called ramping capability, as the need for this service will increase with more renewable energy penetration on the power system.

alpha-Synuclein aggregation in neurodegenerative diseases and its inhibition as a potential therapeutic strategy

There is strong evidence for the involvement of alpha-synuclein in the pathologies of several neurodegenerative disorders, including PD (Parkinson's disease). Development of disease appears to be linked to processes that increase the rate at which alpha-synuclein forms aggregates. These processes include increased protein concentration (via either increased rate of synthesis or decreased rate of degradation), and altered forms of alpha-synuclein (such as truncations, missense mutations, or chemical modifications by oxidative reactions). Aggregated forms of the protein are toxic to cells and one therapeutic strategy would be to reduce the rate at which aggregation occurs. To this end we have designed several peptides that reduce alpha-synuclein aggregation. A cell-permeable version of one such peptide was able to inhibit the DNA damage induced by Fe(II) in neuronal cells transfected with alpha-synuclein (A53T), a familial PD-associated mutation.

alpha-Synuclein aggregation

Alpha-synuclein is a major component of Lewy bodies in Parkinson's disease and is found associated with several other forms of dementia. As with other neurodegenerative diseases, the ability of alpha-synuclein to aggregate and form fibrillar deposits seems central to its pathology. We have defined a sequence within the NAC region of alpha-synuclein that is necessary for aggregation. Exploitation of chemically modified analogues of this peptide may produce inhibitors of aggregation.

Aggregation and neurotoxicity of alpha-synuclein and related peptides

Fibrillar deposits of alpha-synuclein occur in several neurodegenerative diseases. Two mutant forms of alpha-synuclein have been associated with early-onset Parkinson's disease, and a fragment has been identified as the non-amyloid-beta peptide component of Alzheimer's disease amyloid (NAC). Upon aging, solutions of alpha-synuclein and NAC change conformation to beta-sheet, detectable by CD spectroscopy, and form oligomers that deposit as amyloid-like fibrils, detectable by electron microscopy. These aged peptides are also neurotoxic. Experiments on fragments of NAC have enabled the region of NAC responsible for its aggregation and toxicity to be identified. NAC(8-18) is the smallest fragment that aggregates, as indicated by the concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. Fragments NAC(8-18) and NAC(8-16) are toxic, whereas NAC(12-18), NAC(9-16) and NAC(8-15) are not. Hence residues 8-16 of NAC comprise the region crucial for toxicity. Toxicity induced by alpha-synuclein, NAC and NAC(1-18) oligomers occurs via an apoptotic mechanism, possibly initiated by oxidative damage, since these peptides liberate hydroxyl radicals in the presence of iron. Molecules with anti-aggregational and/or antioxidant properties may therefore be potential therapeutic agents.

Identification of the region of non-A beta component (NAC) of alzheimer's disease amyloid responsible for its aggregation and toxicity

The non-beta-amyloid (Aß) component of Alzheimer's disease amyloid (NAC) and its precursor a-synuclein have been linked to amyloidogenesis in several neurodegenerative diseases. NAC and a-synuclein both form ß-sheet structures upon ageing, aggregate to form fibrils, and are neurotoxic. We recently established that a peptide comprising residues 3±18 of NAC retains these properties. To pinpoint the exact region responsible we have carried out assays of toxicity and physicochemical properties on smaller fragments of NAC. Toxicity was measured by the ability of fresh and aged peptides to inhibit the reduction of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) by rat pheochromocytoma PC12 cells and human neuroblastoma SHSY-5Y cells. On immediate dissolution, or after ageing, the fragments NAC(8±18) and NAC(8±16) are toxic, whereas NAC(12±18), NAC(9±16) and NAC(8±15) are not. Circular dichroism indicates that none of the peptides displays ß-sheet structure; rather all remain random coil throughout 24 h. However, in acetonitrile, an organic solvent known to induce ß sheet, fragments NAC(8±18) and NAC(8±16) both form ß-sheet structure. Only NAC(8±18) aggregates, as indicated by concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. These findings indicate that residues 8±16 of NAC, equivalent to residues 68±76 in a-synuclein, comprise the region crucial for toxicity.

An Investigation of the Flow Field through a Variable Geometry Turbine Stator with Vane Endwall Clearance

Variable geometry turbines provide an extra degree of flexibility in air management in turbocharged engines. The pivoting stator vanes used to achieve the variable turbine geometry necessitate the inclusion of stator vane endwall clearances. The consequent leakage flow through the endwall clearances impacts the flow in the stator vane passages and an understanding of the impact of the leakage flow on stator loss is required. A numerical model of a typical variable geometry turbine was developed using the commercial CFX-10 computational fluid dynamics software, and validated using laser doppler velocimetry and static pressure measurements from a variable geometry turbine with stator vane endwall clearance. Two different stator vane positions were investigated, each at three different operating conditions representing different vane loadings. The vane endwall leakage was found to have a significant impact on the stator loss and on the uniformity of flow entering the turbine rotor. The leakage flow changed considerably at different vane positions and flow incidence at vane inlet was found to have a significant impact.