Electron beam evaporation of superconductor-ferromagnet heterostructures.

We report on the electronic and magnetic properties of superconductor-ferromagnet heterostructures fabricated by electron beam evaporation on to unheated thermally oxidised Si substrates. Polycrystalline Nb thin films (5 to 50 nm thick) were shown to possess reliably high superconducting critical temperatures ([Formula: see text]), which correlate well with the residual resistivity ratio (RRR) of the film. These properties improved during ex-situ annealing, resulting in [Formula: see text] and [Formula: see text]RRR increases of up 2.2 K ([Formula: see text] 40% of the pre-annealed [Formula: see text]) and 0.8 ([Formula: see text] 60% of the pre-annealed RRR) respectively. Nb/Pt/Co/Pt heterostructures showed substantial perpendicular anisotropy in the ultrathin limit (≤ 2.5 nm), even in the extreme limit of Pt(0.8 nm)/Co(1 nm)/Pt(0.6 nm). These results point to the use of electron beam evaporation as route to line-of-sight deposited, low-thickness, high quality Nb-based superspintronic multilayers.

Investigating cue competition in contextual cuing of visual search.

A fundamental principle of learning is that predictive cues or signals compete with each other to gain control over behavior. Associative and propositional reasoning theories of learning provide radically different accounts of cue competition. Propositional accounts predict that under conditions that do not afford or warrant the use of higher order reasoning processes, cue competition should not be observed. We tested this prediction in 2 contextual cuing experiments, using a visual search task in which patterns of distractor elements predict the location of a target object. Blocking designs were used in which 2 sets of predictive distractors were trained in compound, with 1 set trained independently. There was no evidence of cue competition in either experiment. In fact, in Experiment 2, we found evidence for augmentation of learning. The findings are contrasted with the predictions of an error-driven associative model of contextual cuing (Brady & Chun, 2007).

Drug cue induced overshadowing: selective disruption of natural reward processing by cigarette cues amongst abstinent but not satiated smokers.

BACKGROUND: Addicts show both reward processing deficits and increased salience attribution to drug cues. However, no study to date has demonstrated that salience attribution to drug cues can directly modulate inferences of reward value to non-drug cues. Associative learning depends on salience: a more salient predictor of an outcome will 'overshadow' a less salient predictor of the same outcome. Similarly, blocking, a demonstration that learning depends on prediction error, can be influenced by the salience of the cues employed. METHOD: This study investigated whether salient drug cues might interact with neutral cues predicting financial reward in an associative learning task indexing blocking and overshadowing in satiated smokers (n=24), abstaining smokers (n=24) and non-smoking controls (n=24). Attentional bias towards drug cues, craving and expired CO were also indexed. RESULTS: Abstaining smokers showed drug cue induced overshadowing, attributing higher reward value to drug cues than to neutral cues that were equally predictive of reward. Overshadowing was positively correlated with expired CO levels, which, in turn, were correlated with craving in abstainers. An automatic attentional bias towards cigarette cues was found in abstainers only. CONCLUSIONS: These findings provide the first evidence that drug cues interact with reward processing in a drug dependent population.

The influence of blocking on overt attention and associability in human learning.

Previous studies have demonstrated a retardation in the rate of novel learning about previously blocked cues as compared to appropriate control cues. We report an experiment investigating whether this retardation in novel learning about a blocked cue is accompanied by a reduction in attention to this cue, as anticipated by attentional theories of associative learning. Consistent with these theories, eye gaze measures revealed a reduction in overt attention to the blocked cue both during the compound training phase of the blocking procedure, and also during novel learning with respect to new outcomes. Moreover, the extent of the bias in overt attention away from blocked cues was positively correlated with the subsequent reduction in rate of novel learning about these cues.

Syntactic transfer in artificial grammar learning.

In an artificial grammar learning (AGL) experiment, participants were trained with instances of one grammatical structure before completing a test phase in which they were required to discriminate grammatical from randomly created strings. Importantly, the underlying structure used to generate test strings was different from that used to generate the training strings. Despite the fact that grammatical training strings were more similar to nongrammatical test strings than they were to grammatical test strings, this manipulation resulted in a positive transfer effect, as compared with controls trained with nongrammatical strings. It is suggested that training with grammatical strings leads to an appreciation of set variance that aids the detection of grammatical test strings in AGL tasks. The analysis presented demonstrates that it is useful to conceptualize test performance in AGL as a form of unsupervised category learning.

The effect of predictive history on the learning of sub-sequence contingencies.

Two experiments demonstrated that the prior predictive history of a cue governs the extent to which that cue engages in sequence learning. Using a serial reaction time task, we manipulated the predictiveness of the stimulus locations (cues) with respect to the location of the stimulus on the next trial (outcome), such that half of the cues were good predictors of their outcomes, whilst the other half were poorer predictors. Following this, all cues were then paired with novel outcomes. Learning about those cues that were previously established as good predictors proceeded more rapidly than learning for those cues previously established as poor predictors. When the simple recurrent network is modified to include a variable associability parameter, the effects are easily modelled.

Learned predictiveness effects in humans: a function of learning, performance, or both?

Many previous studies of animal and human learning indicate a processing advantage for cues previously experienced as good predictors of outcomes over those experienced as poorer predictors. Four studies of human associative learning investigated whether learned predictiveness acts at the level of learning (modulating the rate at which cue-outcome associations form), performance (modulating the strength of behavioral responses), or both. In Experiments 1-3, it was found that retrospectively altering the learned predictiveness of cues influenced responding to those cues, demonstrating that learned predictiveness influences performance. Experiment 4 indicates that learned predictiveness also influences learning by demonstrating that the learned predictiveness of a cue affects the acquisition of an association between a novel cue and the outcome with which it is paired.

Blocking of human causal learning involves learned changes in stimulus processing.

Several theories of associative learning propose that blocking reflects changes in the processing devoted to learning about cues. The results of the only direct test of this suggestion in human learning (Kruschke & Blair, 2000) could equally well be explained in terms of, among others, interference in learning or memory. The present study tested this suggestion in a situation in which processing-change and interference accounts predict opposing results. Results support the idea that blocking in human learning can reflect a change in processing of the cues involved.

A systematic analysis of PCR contamination.

In light of the strict legal scrutiny surrounding DNA typing at this time, it has become necessary to systematically address the issue of PCR contamination. To precisely define the parameters affecting PCR contamination under casework analysis conditions, PCR amplification reactions were intentionally compromised by employing sub-standard laboratory technique and by introducing secondary sources of DNA. The PCR parameters considered for potential sources of contamination include amplification set-up, amplification product handling, aerosol DNA and storage. In addition, analyst technique was evaluated by modifying or eliminating standard safeguards. Under the circumstances normally encountered during casework analysis, PCR contamination was never noted. Significantly, using the dot blot detection method, contamination was never observed when nanogram quantities of genomic DNA were mishandled or aerosolized. Contamination occurred only when amplification product was carelessly manipulated or purposefully sprayed near or directly into open tubes containing water or genomic DNA. Although standard precautions should be employed during PCR-based DNA typing, our data indicates that contamination during amplification procedures is not prevalent when detected by dot blot analysis.

The first EGF-like domain from human factor IX contains a high-affinity calcium binding site.

It has been suggested that epidermal growth factor-like (EGF-like) domains, containing conserved carboxylate residues, are responsible for the high-affinity calcium binding exhibited by a number of vitamin K-dependent plasma proteins involved in the control of the blood coagulation cascade. These include the procoagulant factors IX and X, and the anticoagulants protein C and protein S. To test this hypothesis we have expressed the first EGF-like domain from human factor IX (residues 46-84) using a yeast secretion system, and examined calcium binding to the domain. Using 1H-NMR to measure a calcium-dependent shift assigned to Tyr69 we have detected a high-affinity calcium binding site (Kd = 200-300 microM). We suggest that other EGF-like domains of this type may have similar calcium binding properties. In addition, we have completely assigned the aromatic region of the NMR spectrum by NOESY and COSY analysis, and have used these data to discuss the effect of calcium and pH on the conformation of the domain with reference to a model based on the structure of human EGF.

Cyclodextrin chiral stationary phases for liquid chromatographic separations of drug stereoisomers.

Many active drugs are racemic mixtures. Because the two enantiomers of a racemate often cause different pharmacological responses, the use of optically pure isomers is desirable and may be soon required. Cyclodextrin-bonded silica gel can be used as chiral stationary phase (CSP) in liquid chromatography. The enantiomers of 25 different racemic drugs were separated on such CSPs in the reversed-phase mode. The principal features of the cyclodextrin chiral recognition mechanism are recalled and some information on future trends for cyclodextrin CSPs is provided.

Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes.

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.

The inhibition of class C beta-lactamases by boronic acids.

Aromatic boronic acids are reversible inhibitors of the recently classified class C beta-lactamases. The boronic acids studied include ortho-, meta- and para-methyl-, -hydroxymethyl- and -formyl-phenylboronic acid. The beta-lactamases were chromosomally-encoded enzymes, one from Pseudomonas aeruginosa, and the other specified by the ampC gene of Escherichia coli. The inhibition may be correlated with our finding that these beta-lactamases are serine enzymes, i.e. their function entails the hydroxy group of a serine residue acting as a nucleophile.