title: Total site targeting with stream specific minimum temperature difference

authors: Fodor, Zsófia

subjects: Exchanger area

abstract: The paper focuses on extending traditional Total Site Integration methodology to produce more meaningful utility and heat recovery targets for the process design. The traditional methodology leads to inadequate results due to inaccurate estimation of the overall Total Site heat recovery targets. The new methodology is a further development of a recently extended traditional pinch methodology. The previous extension was on the introduction of using an individual minimum temperature difference (δTmin) for different processes so that the δTmin is more representative of the specific process. Further this paper deals with stream specific δT min inside each process by setting different δT contribution (δTcont) and also using different δTcont between the process streams and the utility systems. The paper describes the further extended methodology called stream specific targeting methodology. A case study applying data from a real diary factory is used to show the differences between the traditional, process specific and stream specific total site targeting methodologies. The extended methodology gives more meaningful results at the end of the targeting with this avoiding the over or under estimated heat exchanger areas in the process design.

text: Total site targeting with stream specific minimum temperature difference The paper focuses on extending traditional Total Site Integration methodology to produce more meaningful utility and heat recovery targets for the process design. The traditional methodology leads to inadequate results due to inaccurate estimation of the overall Total Site heat recovery targets. The new methodology is a further development of a recently extended traditional pinch methodology. The previous extension was on the introduction of using an individual minimum temperature difference (δTmin) for different processes so that the δTmin is more representative of the specific process. Further this paper deals with stream specific δT min inside each process by setting different δT contribution (δTcont) and also using different δTcont between the process streams and the utility systems. The paper describes the further extended methodology called stream specific targeting methodology. A case study applying data from a real diary factory is used to show the differences between the traditional, process specific and stream specific total site targeting methodologies. The extended methodology gives more meaningful results at the end of the targeting with this avoiding the over or under estimated heat exchanger areas in the process design.

year: 2012

title: pH-sensitive Anticancer Model Prodrug: Amide of Kemp's Acid

authors: Brooks, Robert Turongo

subjects: Anticancer Model prodrug

abstract: Solid tumours are characterised by lower extracellular pH (as low as 5.8 pH) compared to normal healthy cellular pH (actively regulated at pH 7.3). This difference may be exploited with an acid-sensitive anti-tumour prodrug which releases a cytotoxin selectively in tumour tissue.
The research reported in this thesis was aimed at synthesising and performing rate studies on an amide prodrug with pH-sensitive rates of reaction in the pH 5 - 8 region. Amide hydrolysis is catalysed by neighbouring carboxylic acid groups in their fully protonated state but not in its ionised state (shown in the figure below), whereby pH sensitivity around pH 5 - 8 can be exploited. The current study was carried out on an amide of Kemp's acid which, due to enforced stereochemistry of carboxylic acid and amide functional groups, has the type of structure conducive to accelerated amide hydrolysis.
The rates for tertiary and secondary aliphatic amides of this Kemp's acid system have shown high reactivity at low pH and a large reduction in rate across pH 5.8 - 7.3, however an aryl amide had not previously been studied. It was thought that an aryl amide of Kemp's acid would provide a faster rate of reaction compared with the alkyl amides, and also aryl amine cytotoxins exist which could be attached as an amide.
A secondary aryl amide of Kemp's acid (58) was obtained via a potassium hydroxide ring-opening reaction on a synthesised imide of Kemp's acid (43).
Aliquots of the ring-opened amide (58) were added to buffered (phosphate and malonate) aqueous solutions (with ionic strength μ = 1 mol L-1) and the hydrolysis reaction followed at 30.0 oC across the pH range 0.48 - 8. First order rate constants were calculated from absorbance change with time and the pH-rate profile established. Absorbance changes were shown to be consistent with amide hydrolysis with no evidence of any imide reformation as evident in other studies. The rate data were analysed. There was no evidence from rates for the two successive acid ionisations with only a single rate plateau evident from pH 2 to 5, suggesting that both
ONHCOOHCOO-OMe(58)
iv
di- and mono-acid species have very similar hydrolysis rates or that the second ionisation is low due to stabilisation of the mono-ionised molecule by hydrogen bonding interactions. For this reason, the rate profile could be analysed only as if it were a single ionisation in the same way that Menger and Ladika analysed their aliphatic tertiary pyrrolidyl amide in an earlier study. This analysis gave a pKa value of 6.72   0.09 and a limiting rate constant of 7.1 x 10-5 s-1. The studies revealed a three fold rate differential between pH 5.8 (faster) versus 7.3 (slower), a difference which is probably too small a selectivity for possible prodrug application.
Separately, the second order rate coefficient for the reaction of potassium hydroxide solution to open the imide was also established (k2 = 0.00067 L mol-1 s-1 at 30.0 oC, μ = 1.00 mol L-1 with KCl).

text: pH-sensitive Anticancer Model Prodrug: Amide of Kemp's Acid Solid tumours are characterised by lower extracellular pH (as low as 5.8 pH) compared to normal healthy cellular pH (actively regulated at pH 7.3). This difference may be exploited with an acid-sensitive anti-tumour prodrug which releases a cytotoxin selectively in tumour tissue.
The research reported in this thesis was aimed at synthesising and performing rate studies on an amide prodrug with pH-sensitive rates of reaction in the pH 5 - 8 region. Amide hydrolysis is catalysed by neighbouring carboxylic acid groups in their fully protonated state but not in its ionised state (shown in the figure below), whereby pH sensitivity around pH 5 - 8 can be exploited. The current study was carried out on an amide of Kemp's acid which, due to enforced stereochemistry of carboxylic acid and amide functional groups, has the type of structure conducive to accelerated amide hydrolysis.
The rates for tertiary and secondary aliphatic amides of this Kemp's acid system have shown high reactivity at low pH and a large reduction in rate across pH 5.8 - 7.3, however an aryl amide had not previously been studied. It was thought that an aryl amide of Kemp's acid would provide a faster rate of reaction compared with the alkyl amides, and also aryl amine cytotoxins exist which could be attached as an amide.
A secondary aryl amide of Kemp's acid (58) was obtained via a potassium hydroxide ring-opening reaction on a synthesised imide of Kemp's acid (43).
Aliquots of the ring-opened amide (58) were added to buffered (phosphate and malonate) aqueous solutions (with ionic strength μ = 1 mol L-1) and the hydrolysis reaction followed at 30.0 oC across the pH range 0.48 - 8. First order rate constants were calculated from absorbance change with time and the pH-rate profile established. Absorbance changes were shown to be consistent with amide hydrolysis with no evidence of any imide reformation as evident in other studies. The rate data were analysed. There was no evidence from rates for the two successive acid ionisations with only a single rate plateau evident from pH 2 to 5, suggesting that both
ONHCOOHCOO-OMe(58)
iv
di- and mono-acid species have very similar hydrolysis rates or that the second ionisation is low due to stabilisation of the mono-ionised molecule by hydrogen bonding interactions. For this reason, the rate profile could be analysed only as if it were a single ionisation in the same way that Menger and Ladika analysed their aliphatic tertiary pyrrolidyl amide in an earlier study. This analysis gave a pKa value of 6.72   0.09 and a limiting rate constant of 7.1 x 10-5 s-1. The studies revealed a three fold rate differential between pH 5.8 (faster) versus 7.3 (slower), a difference which is probably too small a selectivity for possible prodrug application.
Separately, the second order rate coefficient for the reaction of potassium hydroxide solution to open the imide was also established (k2 = 0.00067 L mol-1 s-1 at 30.0 oC, μ = 1.00 mol L-1 with KCl).

year: 2009

title: “You’re not coming out – you’ve been there all along and just no one’s looked”: Māori LGBT+ youth and identity exploration

authors: Laurence, Rebekah

subjects: Māori

abstract: This research is a Masters-level project on Māori LGBT-plus (lesbian, gay, bisexual, transgender, and other) youths’ experience of exploring their gender and sexual identities, highlighting how whānau (loosely, ‘extended family’) can provide mana (authority, power) such that youth can exercise mana rangatiratanga (a Maniapoto description of ‘autonomy, self-determination’) regarding their identities. This is a novel, exploratory study.
Adapted elements from a Mana Wāhine (Māori feminist) perspective of Kaupapa Māori theory comprised the theoretical framework for this project. These elements were Mana rangatiratanga (adapted from Tino rangatiratanga), Te reo Māori me ōna tikanga (Māori language and its culture), and Whanaungatanga (relationships). The three elements were adapted to fit a Ngāti Maniapoto worldview. 
Qualitative research methods were used for this study. There were five participants aged between 17 and 24 years, who were Māori and had diverse gender or sexual identities. Semi-structured, face-to-face interviews were conducted with participants, which allowed them to share their experiences of exploring their gender and sexual identities and of whānau support. Interviews were analysed using a process of inductive thematic analysis, which identified and analysed patterns across the dataset.
Eight themes were derived from participants’ experiences. These themes were Ko Tūhura, which described the process of discovery that participants have experienced; Ko Matatapu, which described participants’ experience of authenticity and concealment of their gender and sexual identities; Ko Tautoko, which described how whānau have empowered participants to explore their identities, and how participants have been denied empowerment; Ko Mata-ngaro, which described participants’ early lack of exposure to diverse identities, and their having their identities unseen by others; Ko te Ahunga-ki-te-aunoa, which described how diverse identities have been accepted within participants’ whānau; Ko Tauawhi, which described how participants have been embraced for their diverse identities; Ko Mata-pū-take, which describes participants’ experience of finding somewhere to belong; and Ko Kiritau, which describes participants’ becoming settled in their expression of their gender and sexual identities.
The findings of the thesis describe roles that whānau play in participants’ exploration of their gender and sexual identities and some of the effects that colonisation has had within participants’ whānau regarding their gender and sexual identities. Nonetheless, participants actively resisted these aspects of colonisations and found ways to give voice to their gender and sexual identities.
Given that participants shared that there was a dearth of information regarding gender and sexual identities available to them within their whānau and school environments, organisations within psychology and related fields may work to proactively provide all young Māori people and their whānau with information regarding diverse gender and sexual identities. Moreover, to address the dearth of resources designed for Māori LGBT-plus youth, New Zealand-based researchers may collate information specifically regarding Māori LGBT-plus youth experience of identity exploration and Māori knowledges regarding gender and sexual identities. This information may be collated in community-based resources that are designed specifically for members of this group and their whānau, and professionals who work for them.

text: “You’re not coming out – you’ve been there all along and just no one’s looked”: Māori LGBT+ youth and identity exploration This research is a Masters-level project on Māori LGBT-plus (lesbian, gay, bisexual, transgender, and other) youths’ experience of exploring their gender and sexual identities, highlighting how whānau (loosely, ‘extended family’) can provide mana (authority, power) such that youth can exercise mana rangatiratanga (a Maniapoto description of ‘autonomy, self-determination’) regarding their identities. This is a novel, exploratory study.
Adapted elements from a Mana Wāhine (Māori feminist) perspective of Kaupapa Māori theory comprised the theoretical framework for this project. These elements were Mana rangatiratanga (adapted from Tino rangatiratanga), Te reo Māori me ōna tikanga (Māori language and its culture), and Whanaungatanga (relationships). The three elements were adapted to fit a Ngāti Maniapoto worldview. 
Qualitative research methods were used for this study. There were five participants aged between 17 and 24 years, who were Māori and had diverse gender or sexual identities. Semi-structured, face-to-face interviews were conducted with participants, which allowed them to share their experiences of exploring their gender and sexual identities and of whānau support. Interviews were analysed using a process of inductive thematic analysis, which identified and analysed patterns across the dataset.
Eight themes were derived from participants’ experiences. These themes were Ko Tūhura, which described the process of discovery that participants have experienced; Ko Matatapu, which described participants’ experience of authenticity and concealment of their gender and sexual identities; Ko Tautoko, which described how whānau have empowered participants to explore their identities, and how participants have been denied empowerment; Ko Mata-ngaro, which described participants’ early lack of exposure to diverse identities, and their having their identities unseen by others; Ko te Ahunga-ki-te-aunoa, which described how diverse identities have been accepted within participants’ whānau; Ko Tauawhi, which described how participants have been embraced for their diverse identities; Ko Mata-pū-take, which describes participants’ experience of finding somewhere to belong; and Ko Kiritau, which describes participants’ becoming settled in their expression of their gender and sexual identities.
The findings of the thesis describe roles that whānau play in participants’ exploration of their gender and sexual identities and some of the effects that colonisation has had within participants’ whānau regarding their gender and sexual identities. Nonetheless, participants actively resisted these aspects of colonisations and found ways to give voice to their gender and sexual identities.
Given that participants shared that there was a dearth of information regarding gender and sexual identities available to them within their whānau and school environments, organisations within psychology and related fields may work to proactively provide all young Māori people and their whānau with information regarding diverse gender and sexual identities. Moreover, to address the dearth of resources designed for Māori LGBT-plus youth, New Zealand-based researchers may collate information specifically regarding Māori LGBT-plus youth experience of identity exploration and Māori knowledges regarding gender and sexual identities. This information may be collated in community-based resources that are designed specifically for members of this group and their whānau, and professionals who work for them.

year: 2020