Antibiotic combinations to tackle Gram-negative bacterial pathogens : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry at Massey University, Manawatu Campus, New Zealand

Antimicrobial resistance, especially in Gram-negative bacterial pathogens, is one of the most serious threats with which humans have been confronted. Coordinated efforts from industrial, academic and government sectors have been called and executed to introduce novel antibiotics into the market to meet clinical demand. Despite that, the rate of successful antibiotic development appears to be lagging behind the emergence of antibiotic resistant pathogens in the arms race between humans and super-bugs. In this dire context, alternative approaches are required to tackle Gram-negative bacterial infections. This thesis reports synergistic interaction between a secondary bile salt, sodium deoxycholate (DOC), and 5-nitrofuran pro-drugs, an old class of synthetic antibiotics, in inhibiting/killing Gram-negative enterobacteria, such as Escherichia coli, Salmonella enterica and Citrobacter gillenii. Using a genetic approach, the underlying mechanism of the synergy between the two drugs was found to involve 5-nitrofuran-mediated inhibition of TolC-associated efflux pumps that otherwise exclude DOC from bacterial cells. This synergistic combination provides a promising tool to combat infections caused by enterobacterial pathogens. The mechanism of action of individual drugs, DOC and 5-nitrofurans, was also investigated using whole-genome sequence analyses of selected resistant mutants, followed by genetic and biochemical studies. A novel nitrofuran-activating enzyme, AhpF, was identified in E. coli that reduces 5-nitrofuran prodrugs in a manner different from that of an established 5-nitrofuran activation enzyme NfsB. This discovery opens new avenues to counteract nitrofuran-resistant clinical isolates by screening for molecules that upregulate AhpF expression or catalytic activity, or designing nitrofuran analogues activated at high efficiency by the AhpF enzyme. Also, this thesis identified mutations that cause a low-level resistance to DOC in efflux-pump-deficient genetic background. These all resulted in growth-slowing phenotype, the majority of which were involved in cAMP signaling. Singe mutations conferring high-level DOC-resistance were not identified in the mutant screen, supporting the use of DOC/nitrofuran combinations

The growth of ICT4D:impact in educational system in developing countries

Abstract. Problems in developing countries have been an issue for a long time. ICT4D was initiated to solve these problems, at least to ease the current problems to make living standard a bit better. ICT4D stands for information and communication for development, which uses advanced technology to bring opportunities for the people in many fields, such as in education. The term “developing countries” is hard to define, since it is defined by people from developed countries, but in this thesis, I will go through the definition and variables that defines the term. People think that money could solve the problem, but in fact it cannot stop the problems, but by using it to educate people, we can make use of the knowledge learned and thus improve people’s future. In this thesis, I will introduce ICT4D and the evolution of ICT4D, what kind of changes it has gone through to become what it is now. I will also define developing countries from few points of views and also defining human development index (HDI) and means for a better living standard. Next, I will talk about the education and how it could improve the living standard when implementing it properly and how ICT4D is having and could have an impact on the education in developing countries. Also, I will introduce few challenges that could be problematic but not impossible to solve and how huge of a digital divide is between developing and development countries. All of these affect the educational system in developing countries, and is considered as a highly important matters in digital economy, fortunately we have many movements such as ICT4D to tackle these issuesTiivistelmä. Kehitysmaiden ongelmat ovat olleet keskusteluaiheena jo pitkään. ICT4D-liike pantiin alulle ratkaisemaan näitä ongelmia tai ainakin helpottamaan nykyisiä ongelmia parantaakseen ihmisten elintasoa hieman paremmaksi. ICT4D tarkoittaa “tietoa ja viestintää kehitykselle”, jonka tarkoituksena on käyttää edistynyttä teknologiaa tarjoamaan mahdollisuuksia ihmisille monilla aloilla, kuten koulutusaloilla. “Kehitysmaat” käsitteenä on vaikea määritellä, sillä sana “kehitysmaat” ovat määritelleet maat, joissa teknologia on nykyaikaista ja arkipäiväistä. Tässä opinnäytetyössä käyn kuitenkin läpi ne muuttujat, jotka määrittelevät kyseisen termin. Monet ajattelevat, että raha voisi ratkaista näitä ongelmia, mutta tämä ei kuitenkaan ole totta, vaikkakin ongelmat helpottuvat hetkeksi, ongelma on vielä olemassa. Vain kouluttamalla ihmisiä ja hyödyntämällä nykyteknologiaa ja oppimaamme tietoa, voimme ratkaista ongelmia kehitysmaissa. Tässä työssä käyn läpi termin ICT4D:n ja sen evoluution, sekä millaisia ​​muutoksia se on käynyt läpi tullakseen sellaiseksi kuin se nyt on. Aion määritellä myös kehitysmaat muutamasta näkökulmasta ja myös inhimillisen kehityksen indeksin (HDI) ja keinoja paremman elintason saavuttamiseksi. Seuraavaksi opinnäytetyössäni puhun koulutuksesta ja kuinka se voisi parantaa kehitysmaiden elintasoa, kun sitä pannaan täytäntöön sopivalla tavalla ja miten ICT4D voi vaikuttaa kehitysmaiden koulutukseen. Aion myös esitellä muutamia haasteita, jotka voivat olla ongelmallisia, mutta joita ei ole mahdotonta ratkaista, ja miten valtava digitaalinen kuilu on kehittyneiden maiden ja kehitysmaiden välillä. Kaikki mainitut asiat vaikuttavat kehitysmaiden koulutusjärjestelmään, ja näitä pidetään erittäin tärkeänä digitaalitalouden aikana, onneksemme meillä on monia liikkeitä, kuten ICT4D, jotka ovat valmiita ratkaisemaan näitä ongelmia

To Know, To Love and To Heal: PhotoStory and Duo-Ethnography as Approaches to Enhancing Social Justice and Self-Actualization in High School Classrooms

This article explores using PhotoStory to promote social justice in the classroom. Interweaving Photovoice (Wang & Burris, 1997) with story-sharing results in PhotoStory, a unique teaching and learning approach that can empower voices of marginalized high school students. Through PhotoStory, we explore possibilities for self-actualization in high schools, where a primary pedagogical goal is to disrupt inequitable social orders and change oppressive behaviors and perceptions. Coming to critical consciousness for both teachers and students is vital, leading to engagement in dialogical pedagogy (Mthethwa-Sommers, 2014). As bell hooks (1994) asserts, oppression emanates in and through differences in relation to sex/gender, class and race. Similarly, Freire (1970) highlights the critical role of literacy skills to equip those who are oppressed to speak truth to power. Contextualized by habitus (Bourdieu, 1986), creators of PhotoStory documentaries come to understand their own and others’ lived experiences, enhancing individual and collective empathy, and promoting healing, offering holistic ways to connect through culturally responsive learning, and flipped and flattened pedagogies. By applying duoethnography (Sawyer & Norris, 2013), three authors, two graduate students and one professor discuss and critique this art-based pedagogical method via experiences of utilizing PhotoStory as an experiential teaching and learning tool. Although the scholars are different in relation to age, status, gender and sexual identities, they are committed to exploring an ethic of care and pedagogical self-actualization that serves our need “to know, to love, and to heal”

The question of quality

Phuong-Thao T. Trinh, Thu-Hien T. Le, Thu-Trang Vuong, Phuong-Hanh Hoang (2019). Chapter 6. The question of quality. In Quan-Hoang Vuong, Trung Tran (Eds.), The Vietnamese Social Sciences at a Fork in the Road (pp. 121–142). Warsaw, Poland: De Gruyter. DOI:10.2478/9783110686081-011. Online ISBN: 9783110686081 © 2019 Sciendo / De Gruyte

MoMA: Momentum Contrastive Learning with Multi-head Attention-based Knowledge Distillation for Histopathology Image Analysis

There is no doubt that advanced artificial intelligence models and high quality data are the keys to success in developing computational pathology tools. Although the overall volume of pathology data keeps increasing, a lack of quality data is a common issue when it comes to a specific task due to several reasons including privacy and ethical issues with patient data. In this work, we propose to exploit knowledge distillation, i.e., utilize the existing model to learn a new, target model, to overcome such issues in computational pathology. Specifically, we employ a student-teacher framework to learn a target model from a pre-trained, teacher model without direct access to source data and distill relevant knowledge via momentum contrastive learning with multi-head attention mechanism, which provides consistent and context-aware feature representations. This enables the target model to assimilate informative representations of the teacher model while seamlessly adapting to the unique nuances of the target data. The proposed method is rigorously evaluated across different scenarios where the teacher model was trained on the same, relevant, and irrelevant classification tasks with the target model. Experimental results demonstrate the accuracy and robustness of our approach in transferring knowledge to different domains and tasks, outperforming other related methods. Moreover, the results provide a guideline on the learning strategy for different types of tasks and scenarios in computational pathology. Code is available at: \url{https://github.com/trinhvg/MoMA}.Comment: Preprin