Theoretical study of the electronic nature of non-stoichiometric metal hydrides

Thesis (Ph.D.)--University of the Witwatersrand, Faculty of Science, 1986

To sue or not to sue? : the present and future of liability actions for breaches of European Community law committed by the domestic authorities.

Available from British Library Document Supply Centre-DSC:DXN049365 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Computationally efficient robust MPC using optimized constraint tightening

A robust model predictive control (MPC) method is presented for linear, time-invariant systems affected by bounded additive disturbances. The main contribution is the offline design of a disturbance-affine feedback gain whereby the resulting constraint tightening is minimized. This is achieved by formulating the constraint tightening problem as a convex optimization problem with the feedback term as a variable. The resulting MPC controller has the computational complexity of nominal MPC, and guarantees recursive feasibility, stability and constraint satisfaction. The advantages of the proposed approach compared to existing robust MPC methods are demonstrated using numerical examples.Comment: Submitted to the 61st IEEE Conference on Decision and Control 202

Automated Assessment of Pavlovian Conditioned Freezing and Shock Reactivity in Mice Using the Video Freeze System

The Pavlovian conditioned freezing paradigm has become a prominent mouse and rat model of learning and memory, as well as of pathological fear. Due to its efficiency, reproducibility and well-defined neurobiology, the paradigm has become widely adopted in large-scale genetic and pharmacological screens. However, one major shortcoming of the use of freezing behavior has been that it has required the use of tedious hand scoring, or a variety of proprietary automated methods that are often poorly validated or difficult to obtain and implement. Here we report an extensive validation of the Video Freeze system in mice, a “turn-key” all-inclusive system for fear conditioning in small animals. Using digital video and near-infrared lighting, the system achieved outstanding performance in scoring both freezing and movement. Given the large-scale adoption of the conditioned freezing paradigm, we encourage similar validation of other automated systems for scoring freezing, or other behaviors

The startled seahorse: is the hippocampus necessary for contextual fear conditioning?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56233/2/davisTICS98.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/56233/1/marenTICS98.pd

Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination

We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.http://deepblue.lib.umich.edu/bitstream/2027.42/56234/1/anagJN99.pd

Scopolamine and Pavlovian fear conditioning in rats: dose-effect analysis

Muscarinic-cholinergic antagonism produces learning and memory deficits in a wide variety of hippocampal-dependent tasks. Hippocampal lesions produce both acquisition deficits and retrograde amnesia of contextual fear (fear of the place of conditioning), but do not impact fear conditioning to discrete cues (such as a tone). In order to examine the effects of muscarinic antagonism in this paradigm, rats were given 0.01 to 100 mg/kg of scopolamine (or methylscopolamine) either before or after a fear conditioning session in which tones were paired with aversive footshocks. Fear to the context and the tone were assessed by measuring freezing in separate tests. It was found that pretraining, but not post-training, scopolamine severely impaired fear conditioning; methylscopolamine was ineffective in disrupting conditioning. Although contextual fear conditioning was more sensitive to cholinergic disruption, high doses of scopolamine also disrupted tone conditioning. Scopolamine did not affect footshock reactivity, but did produce high levels of activity. However, hyperactivity was not directly responsible for deficits in conditioning. It was concluded that scopolamine disrupts CS-US association formation or CS processing, perhaps through an attenuation of hippocampal theta rhythm.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56239/1/anagNPHARM99.pd

An extension of the Rescorla and Wagner Simulator for context conditioning

This paper introduces R&W Simulator version 4, which extends previous work by incorporating context simulation within standard Pavlovian designs. This addition allows the assessment of: (1) context–stimulus competition, by treating contextual cues as ordinary background stimuli present throughout the whole experimental session; (2) summation, by computing compound stimuli with contextual cues as an integrating feature, with and without the addition of specific configural cues; and (3) contingency effects in causal learning. These new functionalities broaden the range of experimental designs that the simulator is able to replicate, such as some recovery from extinction phenomena (e.g., renewal effects). In addition, the new version permits specifying probe trials among standard trials and extracting their values

Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5 signaling in the nucleus accumbens

Intermittent systemic exposure to psychostimulants such as amphetamine leads to several forms of long-lasting behavioral plasticity including non-associative sensitization and associative conditioning. In the nucleus accumbens (NAcc), the protein serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) and its phosphorylation target, the guanine-nucleotide exchange factor kalirin-7 (Kal7), may contribute to the neuroadaptations underlying each of these forms of plasticity. Pharmacological inhibition of Cdk5 in the NAcc prevents the increases in dendritic spine density in this site and enhances the locomotor sensitization normally observed following repeated cocaine. Mice lacking the Kal7 gene display similar phenotypes suggesting that locomotor sensitization and increased NAcc spine density need not be positively correlated. As increases in spine density may relate to the formation of associative memories and both Cdk5 and Kal7 regulate the generation of spines following repeated drug exposure, we hypothesized that either inhibiting Cdk5 or preventing its phosphorylation of Kal7 in the NAcc may prevent the induction of drug conditioning. In the present experiments, blockade in rats of NAcc Cdk5 activity with roscovitine (40 nmol/0.5µl/side) prior to each of 4 injections of amphetamine (1.5 mg/kg; i.p.) prevented the accrual of contextual locomotor conditioning but spared the induction of locomotor sensitization as revealed on tests conducted one week later. Similarly, transient viral expression in the NAcc exclusively during amphetamine exposure of a threonine-alanine mutant form of Kal7 [mKal7(T1590A)] that is not phosphorylated by Cdk5 also prevented the accrual of contextual conditioning and spared the induction of sensitization. These results indicate that Cdk5 phosphorylation of Kal7 in the NAcc is necessary for the formation of context-drug associations potentially through the modulation of dendritic spine dynamics in this site