New blind source estimation methods based on constant modulus criterion

This thesis presents two novel algorithms for blind chancel equalization (BCE) and blind source separation (BSS). Beside these, a general framework for global convergent analysis is proposed. Finally, the open problem of equalising a non-irreducible system is answered by the algorithm proposed in this thesis.

The "refoldability" of selected proteins in ionic liquids as a stabilization criterion, leading to a conjecture on biogenesis

The folding of proteins is usually studied in dilute aqueous solutions of controlled pH, but it has recently been demonstrated that reversible unfolding can occur in other media. Particular stability is conferred on the protein (folded or unfolded) when the process occurs in ‘protic ionic liquids’ (pILs) of controlled proton activity. This activity (‘effective pH’) is determined by the acid and base components of the pIL and is characterized in the present study by the proton chemical shift of the N–H proton. Here we propose a ‘refoldability’ or ‘refolding index’ (RFI) metric for assessing the stability of folded biomolecules in different solvent media, and demarcate high RFI zones in hydrated pIL media using ribonuclease A and hen egg white lysozyme as examples. Then we show that, unexpectedly, the same high RFIs can be obtained in pIL media that are 90% inorganic in character (simple ammonium salts). This leads us to a conjecture related to the objections that have been raised to ‘primordial soup’ theories for biogenesis, objections that are based on the observation that all the bonds involved in biomacromolecule formation are hydrolyzed in ordinary aqueous solutions unless specifically protected. The ingredients for primitive ionic liquids (NH3, CO, HCN, CO2, and water) were abundant in the early earth atmosphere, and many experiments have shown how amino acids could form from them also. Cyclical concentration in evaporating inland seas could easily produce the type of ambient-temperature, non-hydrolyzing, media that we have demonstrated here may be hospitable to biomolecules, and that may be actually encouraging of biopolymer assembly. Thus a plausible variant of the conventional ‘primordial soup’ model of biogenesis is suggested.

Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin-1β

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic–pituitary–adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic–pituitary–adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1β. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic–pituitary–adrenal axis responses to systemic interleukin-1β, we next mapped the effects of similar lesions on interleukin-1β-induced Fos expression in regions previously shown to regulate the hypothalamic–pituitary–adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1β, an outcome that is difficult to reconcile with a simple medial prefrontal cortex–bed nucleus of the stria terminalis–corticotropin-releasing factor cell control circuit.

Medullary neurones regulate hypothalamic corticotropin-releasing factor cell responses to an emotional stressor

Hypothalamic–pituitary–adrenal axis activation is a hallmark of the stress response. In the case of physical stressors, there is considerable evidence that medullary catecholamine neurones are critical to the activation of the paraventricular nucleus corticotropin-releasing factor cells that constitute the apex of the hypothalamic–pituitary–adrenal axis. In contrast, it has been thought that hypothalamic–pituitary–adrenal axis responses to emotional stressors do not involve brainstem neurones. To investigate this issue we have mapped patterns of restraint-induced neuronal c-fos expression in intact animals and in animals prepared with either paraventricular nucleus-directed injections of a retrograde tracer, lesions of paraventricular nucleus catecholamine terminals, or lesions of the medulla corresponding to the A1 or A2 noradrenergic cell groups. Restraint-induced patterns of neuronal activation within the medulla of intact animals were very similar to those previously reported in response to physical stressors, including the fact that most stressor-responsive, paraventricular nucleus-projecting cells were certainly catecholaminergic and probably noradrenergic. Despite this, the destruction of paraventricular nucleus catecholamine terminals with 6-hydroxydopamine did not alter corticotropin-releasing factor cell responses to restraint. However, animals with ibotenic acid lesions encompassing either the A1 or A2 noradrenergic cell groups displayed significantly suppressed corticotropin-releasing factor cell responses to restraint. Notably, these medullary lesions also suppressed neuronal responses in the medial amygdala, an area that is now considered critical to hypothalamic–pituitary–adrenal axis responses to emotional stressors and that is also known to display a significant increase in noradrenaline turnover during restraint.

We conclude that medullary neurones influence corticotropin-releasing factor cell responses to emotional stressors via a multisynaptic pathway that may involve a noradrenergic input to the medial amygdala. These results overturn the idea that hypothalamic–pituitary–adrenal axis response to emotional stressors can occur independently of the brainstem.

Opposing roles for medial and central amygdala in the initiation of noradrenergic cell responses to a psychological stressor

Psychological stressors trigger the activation of medullary noradrenergic cells, an effect that has been shown to depend upon yet-to-be-identified structures located higher in the brain. To test whether the amygdala is important in this regard, we examined the effects of amygdala lesions on noradrenergic cell responses to restraint, and also looked at whether any amygdala cells that respond to restraint project directly to the medulla. Ibotenic acid lesions of the medial amygdala completely abolished restraint-induced Fos expression in A1 and A2 noradrenergic cells. In contrast, lesions of the central amygdala actually facilitated noradrenergic cell responses to restraint. Tracer deposits in the dorsomedial (but not ventrolateral) medulla retrogradely labelled many cells in the central nucleus of the amygdala, but none of these cells expressed Fos in response to restraint. These data suggest for the first time that the medial amygdala is critical to the activation of medullary noradrenergic cells by a psychological stressor whereas the central nucleus exerts an opposing, inhibitory influence upon noradrenergic cell recruitment. The initiation of noradrenergic cell responses by the medial amygdala does not involve a direct projection to the medulla. Accordingly, a relay through some other structure, such as the hypothalamic paraventricular nucleus, warrants careful consideration.

Stressor categorization : acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups

It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous immediate–early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25–30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic–pituitary–adrenal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression in subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as ‘physical’ and ‘psychological’. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.

Rock slope risk analysis based on non-linear failure criterion

The probability of failure of a rock slope is generally estimated by using the Limit Equilibrium Method (LEM) in conjunction with a reliability analysis. Although the LEM is relatively simple and time efficient, recent studies have indicated that using the LEM may overestimate the factor of safety by 21%, when based on a non-linear failure criterion. Fortunately, the solutions presented by Li et al. (2008, 2009) can provide more accurate evaluations for rock slope stability as the numerical upper and lower bound limit analysis methods (2002a, 2002b, 2005) were employed. The advantages of these methods are used in this study to assess the rock slope probability of failure. The motivation is that with more accurate methods to evaluate the factor of safety, more economic designs can be performed.