Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation.

The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ(42) fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ(42). Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect of αB-crystallin on the seeded growth of Aβ fibrils, both in solution and on the surface of a quartz crystal microbalance biosensor, reveal that the binding of αB-crystallin to seed fibrils strongly inhibits their elongation. Because the lag phase in sigmoidal fibril assembly kinetics is dominated by elongation and fragmentation rates, the chaperone mechanism identified here represents a highly effective means to inhibit fibril proliferation. Together with previous observations of αB-crystallin interaction with α-synuclein and insulin fibrils, the results suggest that this mechanism is a generic means of providing molecular chaperone protection against amyloid fibril formation.

COMPARISON OF MILLISECOND ANNEALING OF B IMPLANTS AND ISOTHERMAL ANNEALING FOR TIMES OF A FEW SECONDS.

The annealing behaviour of B implants in the millisecond time regime using a combination of swept line beam and background heating is compared with isothermal annealing with heating cycles of a few seconds. Carrier concentration profiles show that under annealing conditions which restrict diffusion, millisecond processing gives higher activation of B implants than isothermal heating. Transmission electron microscopy shows that millisecond annealing also results in a lower defect density.

Natural actor and belief critic: Reinforcement algorithm for learning parameters of dialogue systems modelled as POMDPs

This article presents a novel algorithm for learning parameters in statistical dialogue systems which are modeled as Partially Observable Markov Decision Processes (POMDPs). The three main components of a POMDP dialogue manager are a dialogue model representing dialogue state information; a policy that selects the system's responses based on the inferred state; and a reward function that specifies the desired behavior of the system. Ideally both the model parameters and the policy would be designed to maximize the cumulative reward. However, while there are many techniques available for learning the optimal policy, no good ways of learning the optimal model parameters that scale to real-world dialogue systems have been found yet. The presented algorithm, called the Natural Actor and Belief Critic (NABC), is a policy gradient method that offers a solution to this problem. Based on observed rewards, the algorithm estimates the natural gradient of the expected cumulative reward. The resulting gradient is then used to adapt both the prior distribution of the dialogue model parameters and the policy parameters. In addition, the article presents a variant of the NABC algorithm, called the Natural Belief Critic (NBC), which assumes that the policy is fixed and only the model parameters need to be estimated. The algorithms are evaluated on a spoken dialogue system in the tourist information domain. The experiments show that model parameters estimated to maximize the expected cumulative reward result in significantly improved performance compared to the baseline hand-crafted model parameters. The algorithms are also compared to optimization techniques using plain gradients and state-of-the-art random search algorithms. In all cases, the algorithms based on the natural gradient work significantly better. © 2011 ACM.

Low temperature (< 100 °c) deposited P-type cuprous oxide thin films: Importance of controlled oxygen and deposition energy

With the emergence of transparent electronics, there has been considerable advancement in n-type transparent semiconducting oxide (TSO) materials, such as ZnO, InGaZnO, and InSnO. Comparatively, the availability of p-type TSO materials is more scarce and the available materials are less mature. The development of p-type semiconductors is one of the key technologies needed to push transparent electronics and systems to the next frontier, particularly for implementing p-n junctions for solar cells and p-type transistors for complementary logic/circuits applications. Cuprous oxide (Cu2O) is one of the most promising candidates for p-type TSO materials. This paper reports the deposition of Cu2O thin films without substrate heating using a high deposition rate reactive sputtering technique, called high target utilisation sputtering (HiTUS). This technique allows independent control of the remote plasma density and the ion energy, thus providing finer control of the film properties and microstructure as well as reducing film stress. The effect of deposition parameters, including oxygen flow rate, plasma power and target power, on the properties of Cu2O films are reported. It is known from previously published work that the formation of pure Cu2O film is often difficult, due to the more ready formation or co-formation of cupric oxide (CuO). From our investigation, we established two key concurrent criteria needed for attaining Cu2O thin films (as opposed to CuO or mixed phase CuO/Cu2O films). First, the oxygen flow rate must be kept low to avoid over-oxidation of Cu2O to CuO and to ensure a non-oxidised/non-poisoned metallic copper target in the reactive sputtering environment. Secondly, the energy of the sputtered copper species must be kept low as higher reaction energy tends to favour the formation of CuO. The unique design of the HiTUS system enables the provision of a high density of low energy sputtered copper radicals/ions, and when combined with a controlled amount of oxygen, can produce good quality p-type transparent Cu2O films with electrical resistivity ranging from 102 to 104 Ω-cm, hole mobility of 1-10 cm2/V-s, and optical band-gap of 2.0-2.6 eV. These material properties make this low temperature deposited HiTUS Cu 2O film suitable for fabrication of p-type metal oxide thin film transistors. Furthermore, the capability to deposit Cu2O films with low film stress at low temperatures on plastic substrates renders this approach favourable for fabrication of flexible p-n junction solar cells. © 2011 Elsevier B.V. All rights reserved.