title: Learning language using genetic algorithms

authors: Smith, Tony C.

subjects: computer science

abstract: Strict pattern-based methods of grammar induction are often frustrated by the apparently inexhaustible variety of novel word combinations in large corpora. Statistical methods offer a possible solution by allowing frequent well-formed expressions to overwhelm the infrequent ungrammatical ones. They also have the desirable property of being able to construct robust grammars from positive instances alone. Unfortunately, the  zero-frequency  problem entails assigning a small probability to all possible word patterns, thus ungrammatical n-grams become as probable as unseen grammatical ones. Further, such grammars are unable to take advantage of inherent lexical properties that should allow infrequent words to inherit the syntactic properties of the class to which they belong. 
This paper describes a genetic algorithm (GA) that adapts a population of hypothesis grammars towards a more effective model of language structure. The GA is statistically sensitive in that the utility of frequent patterns is reinforced by the persistence of efficient substructures. It also supports the view of language learning as a  bootstrapping problem,  a learning domain where it appears necessary to simultaneously discover a set of categories and a set of rules defined over them. Results from a number of tests indicate that the GA is a robust, fault-tolerant method for inferring grammars from positive examples of natural language.

text: Learning language using genetic algorithms Strict pattern-based methods of grammar induction are often frustrated by the apparently inexhaustible variety of novel word combinations in large corpora. Statistical methods offer a possible solution by allowing frequent well-formed expressions to overwhelm the infrequent ungrammatical ones. They also have the desirable property of being able to construct robust grammars from positive instances alone. Unfortunately, the  zero-frequency  problem entails assigning a small probability to all possible word patterns, thus ungrammatical n-grams become as probable as unseen grammatical ones. Further, such grammars are unable to take advantage of inherent lexical properties that should allow infrequent words to inherit the syntactic properties of the class to which they belong. 
This paper describes a genetic algorithm (GA) that adapts a population of hypothesis grammars towards a more effective model of language structure. The GA is statistically sensitive in that the utility of frequent patterns is reinforced by the persistence of efficient substructures. It also supports the view of language learning as a  bootstrapping problem,  a learning domain where it appears necessary to simultaneously discover a set of categories and a set of rules defined over them. Results from a number of tests indicate that the GA is a robust, fault-tolerant method for inferring grammars from positive examples of natural language.

year: 1996

title: Studies toward an optimized synthesis of a Novel Imidazopyridinone DNA-PK Inhibitor

authors: Mora, Daniel A.

abstract: Cancer is a disease of global significance, with cancer rates increasing year on year globally. A key challenge within the treatment of cancer is the cellular response to radiotherapy. When fractionated radiotherapy is targeted at cancerous cells DNA double strand breaks are promoted via free radical formation to induce cellular death. However, cellular responses activate the DNA double strand break repair mechanism to oppose these outcomes. Involved in this mechanism is the DNA-PK enzyme and the Auckland Cancer Society Research Centre (ACSRC) has developed an enzyme inhibitor SN39536 to inhibit the repair mechanism. Core aspects of the project surround the use and optimization of an alternative novel synthetic route to the drug as the original published route was developed allowing for structural diversity as opposed to efficiency.

There are three novel reactions at the beginning of the alternative route leading to a point of convergence with the ACSRC route at an imidazopyridinone intermediate; a nucleophilic aromatic substitution, a base-catalyzed hydrolysis and a Curtius rearrangement. Analogous reactions were originally reported by Astra Zeneca (AZ) with pyrimidine analogues however in this work they have been adapted and optimized for pyridine variants. Post optimization the highest yield achieved for the pyridine substrates were; 85.3% for the nucleophilic aromatic substitution, 89.9% for the base-catalyzed hydrolysis and 69.5% for the Curtius rearrangement. These are comparable to the AZ yields with their pyrimidine analogues however in each case the addition of heat and/or increased reaction times were consistently required to match the AZ yields – highlighting that the novel pyridine substrates are not as activated for these reactions.

The novel route generates the same imidazopyridinone intermediate as the ACSRC route in an overall yield of 53.3%. This is significantly lower than the 70.6% overall yield from the ACSRC route. Despite the novel route being viable for the synthesis of imidazopyridinones we propose it is currently an inferior alternative for the synthesis of SN39536.
A rearrangement of the novel route steps was then attempted to explore if the altered electronics of the substrates aid or diminish the synthetic yield of the novel reactions. We placed the final Buchwald-Hartwig amination of the original syntheses after the initial novel nucleophilic aromatic substitution however, we were unable to optimize this novel cross-coupling beyond a yield of 19.0%. Investigation into the reaction conditions were unable to discern why the cross-coupling was consistently unsuccessful. The limited information from our substrate studies suggests that the substrate for this reaction does not have the correct electronics to undergo the proposed cross-coupling. The 19.0% yield of this reaction currently renders the rearranged novel route an unviable alternative to both previous syntheses.

text: Studies toward an optimized synthesis of a Novel Imidazopyridinone DNA-PK Inhibitor Cancer is a disease of global significance, with cancer rates increasing year on year globally. A key challenge within the treatment of cancer is the cellular response to radiotherapy. When fractionated radiotherapy is targeted at cancerous cells DNA double strand breaks are promoted via free radical formation to induce cellular death. However, cellular responses activate the DNA double strand break repair mechanism to oppose these outcomes. Involved in this mechanism is the DNA-PK enzyme and the Auckland Cancer Society Research Centre (ACSRC) has developed an enzyme inhibitor SN39536 to inhibit the repair mechanism. Core aspects of the project surround the use and optimization of an alternative novel synthetic route to the drug as the original published route was developed allowing for structural diversity as opposed to efficiency.

There are three novel reactions at the beginning of the alternative route leading to a point of convergence with the ACSRC route at an imidazopyridinone intermediate; a nucleophilic aromatic substitution, a base-catalyzed hydrolysis and a Curtius rearrangement. Analogous reactions were originally reported by Astra Zeneca (AZ) with pyrimidine analogues however in this work they have been adapted and optimized for pyridine variants. Post optimization the highest yield achieved for the pyridine substrates were; 85.3% for the nucleophilic aromatic substitution, 89.9% for the base-catalyzed hydrolysis and 69.5% for the Curtius rearrangement. These are comparable to the AZ yields with their pyrimidine analogues however in each case the addition of heat and/or increased reaction times were consistently required to match the AZ yields – highlighting that the novel pyridine substrates are not as activated for these reactions.

The novel route generates the same imidazopyridinone intermediate as the ACSRC route in an overall yield of 53.3%. This is significantly lower than the 70.6% overall yield from the ACSRC route. Despite the novel route being viable for the synthesis of imidazopyridinones we propose it is currently an inferior alternative for the synthesis of SN39536.
A rearrangement of the novel route steps was then attempted to explore if the altered electronics of the substrates aid or diminish the synthetic yield of the novel reactions. We placed the final Buchwald-Hartwig amination of the original syntheses after the initial novel nucleophilic aromatic substitution however, we were unable to optimize this novel cross-coupling beyond a yield of 19.0%. Investigation into the reaction conditions were unable to discern why the cross-coupling was consistently unsuccessful. The limited information from our substrate studies suggests that the substrate for this reaction does not have the correct electronics to undergo the proposed cross-coupling. The 19.0% yield of this reaction currently renders the rearranged novel route an unviable alternative to both previous syntheses.

year: 2025

title: Wrestling with Biculturalism in Social Work Education

authors: Glubb-Smith, Kelly J.

subjects: Bicultural social work

abstract: When approached to write a piece on Donna Awatere’s (1984) book Māori Sovereignty from a social work perspective we seized the opportunity to reconsider her work. Revisiting the text after a 30-year-plus hiatus sparked a series of reflective conversations about how we wrestle with teaching biculturalism and our efficacy in preparing students for bicultural practice realities. This article draws upon our co-constructed narratives about what it means to be a social work educator in a bicultural practice landscape. Social work students graduate into an exceedingly complex practice environment fraught with tension about how to resolve inequities across the micro-to-macro continuum. The focus of this article is how Donna Awatere’s work is reflected in the tensions and responsibilities experienced when socialising students into the bicultural mission of social work practice in Aotearoa (New Zealand).

text: Wrestling with Biculturalism in Social Work Education When approached to write a piece on Donna Awatere’s (1984) book Māori Sovereignty from a social work perspective we seized the opportunity to reconsider her work. Revisiting the text after a 30-year-plus hiatus sparked a series of reflective conversations about how we wrestle with teaching biculturalism and our efficacy in preparing students for bicultural practice realities. This article draws upon our co-constructed narratives about what it means to be a social work educator in a bicultural practice landscape. Social work students graduate into an exceedingly complex practice environment fraught with tension about how to resolve inequities across the micro-to-macro continuum. The focus of this article is how Donna Awatere’s work is reflected in the tensions and responsibilities experienced when socialising students into the bicultural mission of social work practice in Aotearoa (New Zealand).

year: 2023-07-27