Laboratory methods for studying memory blocking and recovery include directed forgetting, retrieval-induced forgetting, and retrieval bias or memory blocking procedures. These methods primarily use word lists. For example, striking, reversible forgetting effects have been reported for both emotional (e.g., expletives) and non-emotional (e.g., tools) categorized lists of words. The present study examined forgetting and recovery of richer, more episodic materials. Participants studied a series of brief narrative passages varying in emotional intensity, such as a vignette involving torture or child abuse (emotional) vs. vignettes about cycling or insects (non-emotional). Free recall of the 1-word titles of the vignettes (e.g., Torture, Cyclist) showed a strong memory blocking effect, and cues from the stories on a subsequent cued recall test reversed the effect. In a second experiment, vignette-related pictures inserted into an incidental picture naming task triggered some recovery of initially forgotten vignettes, as shown on a post-test. Both emotional and non-emotional stories were susceptible to this reversible memory blocking effect.

Individuals with autism often have deficient intraverbal repertoires. Previous research has found success in using a blocked trials procedure to facilitate discrimination training. A previous study (unpublished) from our laboratory extended this procedure to intraverbal training. The current study continued this line of research by exploring the outcomes of probing the criterion performance more frequently. Three children with autism, ages 7-13, participated. Eight question pairs were taught. One question was presented repeatedly until a specified number of consecutive correct responses occurred, then the other question was presented. Contingent on specific mastery criteria, the trial blocks were faded into smaller blocks until the questions were presented in quasi-random order. Between each step, a criterion probe was conducted to determine if further steps were necessary. The procedure has been successful for two of the three participants. Criterion probe performance showed that not all teaching steps were needed every time. The procedure may have facilitated acquisition over time, because the number of trials to mastery generally decreased over successive targets.

M.Med., Orthopaedic Surgery, Faculty of Health Sciences, University of the Witwatersrand, 2010

Research in our laboratory has demonstrated blocked and recovered memories within the context of a controlled experiment. The comparative memory paradigm allows for comparisons of recovered memories, continuous memories, and false memories. Additional research in our laboratory has shown two distinct types of memory errors; semantic based errors which occur due to pre-existing category knowledge, and episodic based errors in which the source of details (list members) are misattributed. Independently, these two lines of research have illuminated basic memory processes, however, they have not been combined previously. That is, the experiments in the present study explore the susceptibility of recovered memories to semantic and episodic based errors relative to continuous memories. Experiment 1 replicated the large blocking and recovery effects previously found by our laboratory. Additionally, it demonstrated that recovered memories were no more prone to semantic based errors than were continuous memories. These errors occurred very infrequently despite the use of materials chosen specifically to induce such errors. Experiment 2 again replicated the large blocking and recovery effects. The equivalent low rate of semantic based errors was also replicated. However, Experiment 2 also revealed that recovered memories were more susceptible to episodic based errors than were continuous memories. This was especially true when the memory block occurred in an interference treatment condition. Finally, post-recall source recognition tests failed to improve memory accuracy. In fact, numerically both semantic based and episodic based errors increased on the source recognition test relative to the cued recall test. Findings are discussed in relation to the source monitoring and fuzzy-trace theories of memory as well as the legal and clinical recovered memory controversy.

Research in our laboratory has demonstrated blocked and recovered memories within the context of a controlled experiment. The comparative memory paradigm allows for comparisons of recovered memories, continuous memories, and false memories. Additional research in our laboratory has shown two distinct types of memory errors; semantic based errors which occur due to pre-existing category knowledge, and episodic based errors in which the source of details (list members) are misattributed. Independently, these two lines of research have illuminated basic memory processes, however, they have not been combined previously. That is, the experiments in the present study explore the susceptibility of recovered memories to semantic and episodic based errors relative to continuous memories. Experiment 1 replicated the large blocking and recovery effects previously found by our laboratory. Additionally, it demonstrated that recovered memories were no more prone to semantic based errors than were continuous memories. These errors occurred very infrequently despite the use of materials chosen specifically to induce such errors. Experiment 2 again replicated the large blocking and recovery effects. The equivalent low rate of semantic based errors was also replicated. However, Experiment 2 also revealed that recovered memories were more susceptible to episodic based errors than were continuous memories. This was especially true when the memory block occurred in an interference treatment condition. Finally, post-recall source recognition tests failed to improve memory accuracy. In fact, numerically both semantic based and episodic based errors increased on the source recognition test relative to the cued recall test. Findings are discussed in relation to the source monitoring and fuzzy-trace theories of memory as well as the legal and clinical recovered memory controversy.

Isocyanates are invaluable bulk chemicals that play a central role in the synthesis of various polymers and provide a key platform for the synthesis of nitrogen-containing molecules such as carbamates and ureas. Unfortunately, isocyanates suffer from high toxicity, low functional group tolerance, and a propensity to undergo deleterious side-reactions. Consequently, blocked (masked) isocyanate derivatives have been the subject of increased interest resulting from their reduced toxicity and exceptional control over isocyanate reactivity. This strategy has largely been relegated to the polymerization literature, although its use in the synthesis of complex urea and carbamate derivatives is well established in synthetic organic chemistry. However, prominent gaps in the blocked isocyanate literature were clear at the outset of this research project. First and foremost, the development of heteroatom-substituted isocyanates, such as N- and O-substituted derivatives, remained relatively scarce despite their potential for the synthesis of important nitrogen-containing derivatives. Furthermore, the additions of carbon-centred nucleophiles on blocked N-, O-, and even C-substituted blocked isocyanates were exceedingly rare. Finally, the use of a blocking group strategy in catalytic transformations of isocyanates remained largely absent from the literature. This was particularly striking given the widespread development of catalytic transformations of isocyanates. As such research efforts began focusing on furthering the development of blocked N-isocyanates as a vital platform for heterocyclic synthesis (chapter 2). Initially, the cascade reactivity of blocked N-iso(thio)cyanates was expanded to incorporate electrophiles such as alkynes (section 2.2). This readily provided access to imidazolone and thiazolidine products. Subsequently, the development of a cascade reaction providing access to 1,2,4-triazin-3(2H)-ones was explored (section 2.3). This provided the first examples of an N-isocyanate cascade which hinged on the use of acid catalysis. Moreover, insight into hydrazone isomerization was gained. Finally, these efforts culminated in the development of cascade reactions providing access to a rare class of 1,2,4-triazinones as well as 5-aminopyridazinones (section 2.4). This provided the first example of a cascade reaction involving a C-C bond formation onto a blocked N-isocyanate derivatives. Furthermore, this development was pivotal in re-focusing attention on the development of general strategies to achieve addition of carbon nucleophiles onto blocked isocyanate derivatives. Towards this end, the development of two strategies to achieve carbon-centred nucleophilic additions on both blocked N- And O-isocyanates were developed (chapter 3). Inspiration from the isocyanate literature led to the development of carboxylic acids as formal carbon nucleophiles (section 3.2). This strategy was found to be quite general for the synthesis of hydroxamates from blocked O-isocyanates. Furthermore, encouraging results were generated on the ability of Grignard reagents to form similar products (section 3.3). Particularly important is the paradigm shift this allows from C-N bond formation to C-C bond formation for the synthesis of hydroxamate derivatives. Furthermore, lead results suggest the potential of this reactivity to translate to blocked N-substituted derivatives, a transformation which had failed with carboxylic acids. Finally, the development of a catalytic amide synthesis from blocked isocyanate precursors was targeted (chapter 4). The use of a blocking group strategy was able to address the current major limitation of isocyanates as amide precursors, that is functional group tolerance (section 4.2). Indeed, a commercially available rhodium catalyst was found to allow efficient amidation of various ambiphilic blocked isocyanate derivatives using arylboroxines as nucleophiles. Mechanistic studies including the use of variable time normalization analysis supported the presence of two alternative kinetic regimes contingent on the reaction conditions employed. Furthermore, these data suggested the success of this transformation, in the case of ambiphilic derivatives, hinged on a rate determining isocyanate release (chapter 4). Finally, initial results strongly support the potential for Boc-carbamates to provide a general platform for amidation in the presence of strong nucleophiles such as primary amines. The potential of a blocking group strategy in catalytic reaction development was further displayed with the development of a palladium catalyzed amidation of blocked derivatives with arylboroxine nucleophiles (section 4.3). Indeed, the use of blocked isocyanates was found to be absolutely key in achieving efficient reactivity with the palladium catalyst. This result, coupled with the sparse reports on blocked isocyanates in catalysis, strongly suggest that the use of such a strategy could allow the development of reactivity otherwise unattainable when using free isocyanates.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第17874号 / 工博第3783号 / 新制||工||1578(附属図書館) / 30694 / 京都大学大学院工学研究科都市社会工学専攻 / (主査)教授 谷口 栄一, 教授 藤井 聡, 教授 清野 純史 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

<p>Beamforming of ultrasound signals in the presence of clutter, or partial aperture blockage by an acoustic obstacle can lead to reduced visibility of the structures of interest and diminished diagnostic value of the resulting image. We propose new beamforming methods to recover the quality of ultrasound images under such challenging conditions. Of special interest are the signals from large apertures, which are more susceptible to partial blockage, and from commercial matrix arrays that suffer from low sensitivity due to inherent design/hardware limitations. A coherence-based beamforming method designed for suppressing the in vivo clutter, namely Short-lag Spatial Coherence (SLSC) Imaging, is first implemented on a 1-D array to enhance visualization of liver vasculature in 17 human subjects. The SLSC images show statistically significant improvements in vessel contrast and contrast-to-noise ratio over the matched B-mode images. The concept of SLSC imaging is then extended to matrix arrays, and the first in vivo demonstration of volumetric SLSC imaging on a clinical ultrasound system is presented. The effective suppression of clutter via volumetric SLSC imaging indicates it could potentially compensate for the low sensitivity associated with most commercial matrix arrays. The rest of the dissertation assesses image degradation due to elements blocked by ribs in a transthoracic scan. A method to detect the blocked elements is demonstrated using simulated, ex vivo, and in vivo data from the fully-sampled 2-D apertures. The results show that turning off the blocked elements both reduces the near-field clutter and improves visibility of anechoic/hypoechoic targets. Most importantly, the ex vivo data from large synthetic apertures indicates that the adaptive weighing of the non-blocked elements can recover the loss of focus quality due to periodic rib structure, allowing large apertures to realize their full resolution potential in transthoracic ultrasound.</p> / Dissertation

Using an allergist task, Uengoer, Lotz and Pearce (2013) found that in a design A+/AX+/BY+/CY-, the blocked cue X was indicated to cause the outcome to a greater extent than the uncorrelated cue Y. This finding has been termed “the redundancy effect” by Pearce and Jones (2015). According to Vogel and Wagner (2017), the redundancy effect “presents a serious challenge for those theories of conditioning that compute learning through a global error-term” (p. 119). One such theory is the Rescorla-Wagner (1972) model, which predicts the opposite result, that Y will have a stronger association with the outcome than X. This thesis explored the basis of the redundancy effect in human causal learning. Evidence from Chapter 2 suggested that the redundancy effect was unlikely to have been due to differences in attention between X and Y. Chapter 3 explored whether differences in participants’ certainty about the causal status of X and of Y contributed to the redundancy effect. Manipulations aimed at disambiguating the effects that X had on the outcome, including outcome-additivity training and low outcome rate, resulted in lower ratings for this cue and a smaller redundancy effect. However, the redundancy effect was still significant with both manipulations, suggesting that while participants’ uncertainty about the causal status of X contributed to it, there may have been other factors. Chapter 4 investigated whether another factor was a lack of inhibition for cue C. In a scenario where inhibition was more plausible than in an allergist task, a negative correlation between causal ratings for C and for Y, and a positive correlation between ratings for C and the magnitude of the redundancy effect, were found. In addition, establishing C as inhibitory resulted in a smaller redundancy effect than establishing C as neutral. Overall, findings of this thesis suggest that the redundancy effect in human causal learning is the result of participants’ uncertainty about the causal status of X, and a lack of inhibition for C. Further work is recommended to explore whether combining manipulations targeting X and Y would reverse the redundancy effect, whether effects of outcome additivity and outcome rate on X are the result of participants’ uncertainty about this cue, and the extent to which participants rely on single versus summed error.

Over the past recent years, β-aminocarbonyls have been of great interest to medicinal chemists. As a practical method to obtain these moieties, alkene aminocarbonylation, accounting for the formation of a C-N and a C-C bond, has been the subject of limited research efforts (very specific intramolecular metal-catalyzed variants have been reported). Direct aminocarbonylation of alkenes constitutes a challenging and an important potential innovation in the synthesis of β-aminocarbonyls such as β-amino acids. The research efforts described in the present thesis have been primarily directed towards the development of concerted pathways for the amination of alkenes using hydrazine derivatives as bifunctional reagents. Building on our previous report on the reactivity of hydrazides, progress on the aminocarbonylation of alkenes along with the synthetic scope of this reactivity are herein provided. Therefore, the first part of the present thesis (Chapter 2) focuses primarily on the development of thermolytic conditions for the intramolecular aminocarbonylation of alkenes using amino-isocyanates. Alongside, development of imino-isocyanates have provided complementary synthetic tools for aminocarbonylation. The second part (Chapter 3) describes the work accomplished towards intermolecular aminocarbonylation of alkenes and the synthesis of complex azomethine imine products (Chapter 3). Finally, the last part of the discussion (Chapter 4) will be on the development of new hydrazide reagents for the intramolecular Cope-type hydroamination of alkenes. In doing so, description of the synthetic utility of amino-isocyanates as amphoteric reagents for cascade reactions and heterocyclic synthesis will be provided.