Multiple discrete soluble aggregates influence polyglutamine toxicity in a Huntington\u27s disease model system

Huntington’s disease (HD) results from expansions of polyglutamine stretches (polyQ) in the huntingtin protein (Htt) that promote protein aggregation, neurodegeneration, and death. Since the diversity and sizes of the soluble Htt-polyQ aggregates that have been linked to cytotoxicity are unknown, we investigated soluble Htt-polyQ aggregates using analytical ultracentrifugation. Soon after induction in a yeast HD model system, non-toxic Htt-25Q and cytotoxic Htt-103Q both formed soluble aggregates 29S to 200S in size. Because current models indicate that Htt-25Q does not form soluble aggregates, reevaluation of previous studies may be necessary. Only Htt-103Q aggregation behavior changed, however, with time. At 6 hr mid-sized aggregates (33S to 84S) and large aggregates (greater than 100S) became present while at 24 hr primarily only mid-sized aggregates (20S to 80S) existed. Multiple factors that decreased cytotoxicity of Htt-103Q (changing the length of or sequences adjacent to the polyQ, altering ploidy or chaperone dosage, or deleting anti-aging factors) altered the Htt-103Q aggregation pattern in which the suite of mid-sized aggregates at 6 hr were most correlative with cytotoxicity. Hence, the amelioration of HD and other neurodegenerative diseases may require increased attention to and discrimination of the dynamic alterations in soluble aggregation processes

Coupling Josephson qubits via a current-biased information bus

Josephson qubits without direct interaction can be effectively coupled by sequentially connecting them to an information bus: a current-biased large Josephson junction treated as an oscillator with adjustable frequency. The coupling between any qubit and the bus can be controlled by modulating the magnetic flux applied to that qubit. This tunable and selective coupling provides two-qubit entangled states for implementing elementary quantum logic operations, and for experimentally testing Bell's inequality.Comment: 10 pages, 1 figure. submitte

Analysis of controlled auto-ignition /HCCI combustion in a direct injection gasoline engine with single and split fuel injections

A multi-cycle three-dimensional CFD engine simulation programme has been developed and applied to analyze the Controlled autoignition (CAI) combustion, also known as homogeneous charge compression ignition (HCCI), in a direct injection gasoline engine. CAI operation was achieved through the negative valve overlap method by means of a set of low lift camshafts. In the first part of the paper, the effect of single injection timing on combustion phasing and underlying physical and chemical processes involved was examined through a series of analytical studies using the multi-cycle 3D engine simulation programme. The analyses showed that early injection into the trapped burned gases of a lean-burn mixture during the negative valve overlap period had a large effect on combustion phasing, due to localized heat release and the production of chemically reactive species. As the injection was retarded to the intake stroke, the charge cooling effect tended to slow down the autoignition process. However, further retard of fuel injection to the compression stroke caused the earlier start of main combustion as fuel stratification was produced in the cylinder. In order to optimize the engine performance and engine-out emissions, double injection was investigated by injecting part of the fuel first in the negative valve overlap period and the rest of fuel during the intake or compression strokes. By varying the fueling of each injection, the best engine performance was obtained with the 50/50 fuel injection split ratio, while the lowest total NOx and soot emissions were seen with the optimal split injection ratio of 10/90