title: Biosensing-by-Learning Direct Targeting Strategy for Enhanced Tumor Sensitization

authors: Chen, Yifan

subjects: Science & Technology

abstract: We propose a novel iterative-optimization-inspired direct targeting strategy (DTS) for smart nanosystems, which harness swarms of externally manipulable nanoswimmers assembled by magnetic nanoparticles (MNPs) for knowledge-aided tumor sensitization and targeting. We aim to demonstrate through computational experiments that the proposed DTS can significantly enhance the accumulation of MNPs in the tumor site, which serve as a contrast agent in various medical imaging modalities, by using the shortest possible physiological routes and with minimal systemic exposure. The epicenter of a tumor corresponds to the global maximum of an externally measurable objective function associated with an in vivo tumor-triggered biological gradient; the domain of the objective function is the tissue region at a high risk of malignancy; swarms of externally controllable magnetic nanoswimmers for tumor sensitization are modeled as the guess inputs. The objective function may be resulted from a passive phenomenon such as reduced blood flow or increased kurtosis of microvasculature due to tumor angiogenesis; otherwise, the objective function may involve an active phenomenon such as the fibrin formed during the coagulation cascade activated by tumor-targeted “activator” nanoparticles. Subsequently, the DTS can be interpreted from the iterative optimization perspective: guess inputs (i.e., swarms of nanoswimmers) are continuously updated according to the gradient of the objective function in order to find the optimum (i.e., tumor) by moving through the domain (i.e., tissue under screening). Along this line of thought, we propose the computational model based on the gradient descent (GD) iterative method to describe the GD-inspired DTS, which takes into account the realistic in vivo propagation scenario of nanoswimmers. By means of computational experiments, we show that the GD-inspired DTS yields higher probabilities of tumor sensitization and more significant dose accumulation compared to the “brute-force” search, which corresponds to the systemic targeting scenario where drug nanoparticles attempt to target a tumor by enumerating all possible pathways in the complex vascular network. The knowledge-aided DTS has potential to enhance the tumor sensitization and targeting performance remarkably by exploiting the externally measurable, tumor-triggered biological gradients. We believe that this work motivates a novel biosensing-by-learning framework facilitated by externally manipulable, smart nanosystems.

text: Biosensing-by-Learning Direct Targeting Strategy for Enhanced Tumor Sensitization We propose a novel iterative-optimization-inspired direct targeting strategy (DTS) for smart nanosystems, which harness swarms of externally manipulable nanoswimmers assembled by magnetic nanoparticles (MNPs) for knowledge-aided tumor sensitization and targeting. We aim to demonstrate through computational experiments that the proposed DTS can significantly enhance the accumulation of MNPs in the tumor site, which serve as a contrast agent in various medical imaging modalities, by using the shortest possible physiological routes and with minimal systemic exposure. The epicenter of a tumor corresponds to the global maximum of an externally measurable objective function associated with an in vivo tumor-triggered biological gradient; the domain of the objective function is the tissue region at a high risk of malignancy; swarms of externally controllable magnetic nanoswimmers for tumor sensitization are modeled as the guess inputs. The objective function may be resulted from a passive phenomenon such as reduced blood flow or increased kurtosis of microvasculature due to tumor angiogenesis; otherwise, the objective function may involve an active phenomenon such as the fibrin formed during the coagulation cascade activated by tumor-targeted “activator” nanoparticles. Subsequently, the DTS can be interpreted from the iterative optimization perspective: guess inputs (i.e., swarms of nanoswimmers) are continuously updated according to the gradient of the objective function in order to find the optimum (i.e., tumor) by moving through the domain (i.e., tissue under screening). Along this line of thought, we propose the computational model based on the gradient descent (GD) iterative method to describe the GD-inspired DTS, which takes into account the realistic in vivo propagation scenario of nanoswimmers. By means of computational experiments, we show that the GD-inspired DTS yields higher probabilities of tumor sensitization and more significant dose accumulation compared to the “brute-force” search, which corresponds to the systemic targeting scenario where drug nanoparticles attempt to target a tumor by enumerating all possible pathways in the complex vascular network. The knowledge-aided DTS has potential to enhance the tumor sensitization and targeting performance remarkably by exploiting the externally measurable, tumor-triggered biological gradients. We believe that this work motivates a novel biosensing-by-learning framework facilitated by externally manipulable, smart nanosystems.

year: 2019

title: Performativity and affectivity: Lesson observations in England's Further Education colleges

authors: Edgington, Ursula

abstract: Teaching and learning observations (henceforth ‘observations’) are commonly used in a broad range of educational environments to assess teaching quality and support professional development. Research centred on observations in England’s Further Education colleges (FE), suggests these strategies are often ineffective because of tensions between ‘authentic’ teaching and the inherent performativity required by some managerialist policies (Ball 2003). This psychosocial study draws on interpretive interactionism (Denzin 1989) to explore lived emotional experiences of FE staff involved in observations and perceptions of embodied ‘performativity’.
 My research involved in-depth semi-biographical interviews with FE staff (n=14) which explored emotional experiences of teaching and learning within the context of their roles as observer and/or observee. Using my personal reflections as an FE teacher, together with my creative writing skills, fictionalised accounts are presented to demonstrate anonymised consolidations of the participants’ narratives (Sparkes 2002). Using conceptual tools from Bourdieu (1991) and the lens of psychoanalysis (Mollon 2002) I draw on Richardson’s (1997) ‘writing as a method of inquiry’ and Ochberg’s (2002) non-linear approach to data analysis to explore shared and disparate themes within the accounts, reflections and fictionalised texts.
 Vocational and personal learning experiences are argued to form a fundamental aspect of the professional habitus of FE staff (James, Biesta 2007). Outcomes from my innovative approach, illuminates this interplay of factors, specifically within the affectivity in the performativity of observations. Hence these findings provide an original contribution to knowledge in this area, by demonstrating how the potential tension in observations is situated in the personal significance of perceptions of an ‘in/authentic self’, rather than the performativity per se. Fictionalisation could be a useful tool to further explore lived emotional experiences of teaching and learning. Indeed, raising awareness of the perceived performativity intrinsic within the affectivity of observations could hold benefits for teaching practice more widely.

text: Performativity and affectivity: Lesson observations in England's Further Education colleges Teaching and learning observations (henceforth ‘observations’) are commonly used in a broad range of educational environments to assess teaching quality and support professional development. Research centred on observations in England’s Further Education colleges (FE), suggests these strategies are often ineffective because of tensions between ‘authentic’ teaching and the inherent performativity required by some managerialist policies (Ball 2003). This psychosocial study draws on interpretive interactionism (Denzin 1989) to explore lived emotional experiences of FE staff involved in observations and perceptions of embodied ‘performativity’.
 My research involved in-depth semi-biographical interviews with FE staff (n=14) which explored emotional experiences of teaching and learning within the context of their roles as observer and/or observee. Using my personal reflections as an FE teacher, together with my creative writing skills, fictionalised accounts are presented to demonstrate anonymised consolidations of the participants’ narratives (Sparkes 2002). Using conceptual tools from Bourdieu (1991) and the lens of psychoanalysis (Mollon 2002) I draw on Richardson’s (1997) ‘writing as a method of inquiry’ and Ochberg’s (2002) non-linear approach to data analysis to explore shared and disparate themes within the accounts, reflections and fictionalised texts.
 Vocational and personal learning experiences are argued to form a fundamental aspect of the professional habitus of FE staff (James, Biesta 2007). Outcomes from my innovative approach, illuminates this interplay of factors, specifically within the affectivity in the performativity of observations. Hence these findings provide an original contribution to knowledge in this area, by demonstrating how the potential tension in observations is situated in the personal significance of perceptions of an ‘in/authentic self’, rather than the performativity per se. Fictionalisation could be a useful tool to further explore lived emotional experiences of teaching and learning. Indeed, raising awareness of the perceived performativity intrinsic within the affectivity of observations could hold benefits for teaching practice more widely.

year: 2013

title: Ko Waipā te awa

authors: Kukutai, Josephine

abstract: This thesis examines the experience of the Ngāti Maniapoto (‘Maniapoto’) iwi in the development and implementation of their river settlement legislation, the Ngā Wai o Maniapoto (Waipā River) Act 2012 (the 'Act’) . The overarching purpose of the Act is to restore and maintain the quality and integrity of the waters that flow into and form part of the Waipā River for present and future generations and the care and protection of the mana tuku iho o Waiwaia. The restoration of the Waipā River is essential because of its considerable significance to Maniapoto. The Waipā River is connected to the health and identity of the Maniapoto people and is a taonga (gift) that contains their spiritual and physical wellbeing. The Waipā River is significant because: 
Te Awa o Waipā is a taonga to Maniapoto; the relationship between Maniapoto and the Waipā River is historical, intellectual, physical, and spiritual; to Maniapoto, their relationship with the Waipā River and their respect for it lies at the heart of their spiritual and physical wellbeing, and their tribal identity and culture
The approach to expressing the journey of Maniapoto in the development and implementation of the Waipā River legislation required a Māori lens. I used a Kaupapa Māori approach to examine the development of the Act and again to understand the difficulties in realising the promise of the Act. The focus of this thesis is on the Maniapoto people and their experience of the Act. The Waipā River Settlement and the Waikato River Settlement are closely connected, and the study delves into the history of the Waikato River Settlement and its influence on the Waipā River Settlement. The rangatiratanga (authority) of Maniapoto within their rohe has always been paramount in decision-making. The co-governance and co-management framework however relies on a different form of decision, that of co-decision-making, which is conducted not only in partnership with the Crown but also other Waikato River iwi. Co-governance and co-management change the standard model of traditional autonomous decision-making or rangatiratanga within an iwi and potentially challenges the decisions made. The co-governance and co-management Deed agreed between Maniapoto and the Crown for the Waipā River has changed how people operate in the Maniapoto rohe and how they may have operated previously. This thesis concludes by reflecting on some of the challenges experienced by Maniapoto in the new co-governance and co-management era.

text: Ko Waipā te awa This thesis examines the experience of the Ngāti Maniapoto (‘Maniapoto’) iwi in the development and implementation of their river settlement legislation, the Ngā Wai o Maniapoto (Waipā River) Act 2012 (the 'Act’) . The overarching purpose of the Act is to restore and maintain the quality and integrity of the waters that flow into and form part of the Waipā River for present and future generations and the care and protection of the mana tuku iho o Waiwaia. The restoration of the Waipā River is essential because of its considerable significance to Maniapoto. The Waipā River is connected to the health and identity of the Maniapoto people and is a taonga (gift) that contains their spiritual and physical wellbeing. The Waipā River is significant because: 
Te Awa o Waipā is a taonga to Maniapoto; the relationship between Maniapoto and the Waipā River is historical, intellectual, physical, and spiritual; to Maniapoto, their relationship with the Waipā River and their respect for it lies at the heart of their spiritual and physical wellbeing, and their tribal identity and culture
The approach to expressing the journey of Maniapoto in the development and implementation of the Waipā River legislation required a Māori lens. I used a Kaupapa Māori approach to examine the development of the Act and again to understand the difficulties in realising the promise of the Act. The focus of this thesis is on the Maniapoto people and their experience of the Act. The Waipā River Settlement and the Waikato River Settlement are closely connected, and the study delves into the history of the Waikato River Settlement and its influence on the Waipā River Settlement. The rangatiratanga (authority) of Maniapoto within their rohe has always been paramount in decision-making. The co-governance and co-management framework however relies on a different form of decision, that of co-decision-making, which is conducted not only in partnership with the Crown but also other Waikato River iwi. Co-governance and co-management change the standard model of traditional autonomous decision-making or rangatiratanga within an iwi and potentially challenges the decisions made. The co-governance and co-management Deed agreed between Maniapoto and the Crown for the Waipā River has changed how people operate in the Maniapoto rohe and how they may have operated previously. This thesis concludes by reflecting on some of the challenges experienced by Maniapoto in the new co-governance and co-management era.

year: 2020