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Environmental Fate and Risk Assessment in Soil of RNAi-based biopesticide dsRNA V-ATPase subunit A against small hive beetle Aethina tumida
Get PDFPhD ThesisPest control is essential for agricultural production. Many conventional pesticides present a risk
for human/animal health and ecological biodiversity because of their environmental persistence
and broad-spectrum action. Thus, the development of novel biopesticides which are less
persistent and more selective in their action, and thus more eco-friendly, represent a promising
avenue for more sustainable food production. However, European Union regulation like (EC)
1107/2009 requires to fully assess the risks of all new active substances.
Double stranded RNA (dsRNA) is a biomolecule that triggers the mechanism of RNA
interference (RNAi), which is a protein synthesis disruptor mechanism in eukaryotic cells.
dsRNA has considerable potential as a tool for selective insect pest control. Analytical protocols
for its extraction, purification and quantification from soil are essential for the tests required to
parameterize environmental fate assessments. This study systematically developed a procedure
for recovering and quantifying dsRNA from loamy sand soil using RT-qPCR. During
adsorption experiments following the OECD 106 Guidelines for Testing of Chemicals, it was
found that pre-equilibrating the soil with CaCl2 solution (0.01M) resulted in precipitation of
dsRNA (CaCl2 solution + dsRNA), because CaCl2 might neutralize the charges on the
phosphate backbone of dsRNA. This enhanced adsorption was compared to soil equilibration
with distilled water. Thus, soil solution composition and ionic strength are important
considerations when following OECD guidelines in assessing the sorption of a new generation
of biopesticides consisting of nucleic acids. In adsorption tests, the dsRNA reached equilibrium
within 1h in loamy sand soil with a sorption coefficient (Kd) 0.55 L kg
-1
. Next, biodegradation
tests in soil were carried out following the OECD 307 guidelines. The experimental data were
fitted with three different biodegradation models (Single First-Order Rate Model, Double FirstOrder in Parallel, First Order Multi-Compartment). The results showed that dsRNA has a short
half-life (DT50) of 10h. This informed an environmental risk assessment in soil for dsRNA
within European legislation EU 1107/2009 which is necessary for the registration of dsRNA as
biopesticide. Furthermore, a new screening test procedure was proposed to identify sensitive
species for biopesticide toxicity by using a bioinformatics tool (BLAST searching in the NCBI
database) to find in the genome of non-target organisms regions of local similarity with the
dsRNA sequence. Overall, it was concluded that even though the dsRNA had a low risk profile
due to its ready biodegradability, considerable uncertainty remains around potentially high
application rates and potential interference of the smaller siRNAs generated from the dsRNA
with mRNA of non-target organisms
The UK equity unit trusts : time-varying market risk and idiosyncratic risk
Get PDFPhD ThesisThis thesis empirically investigates the risk of UK equity unit trusts by breaking down the total risk of trusts into market risk and idiosyncratic risk. This thesis constructs a research sample of 478 UK-authorized equity unit trusts from July 1990 to June 2015, exploring three research questions: the investment abilities of stock-picking and market return-timing; the investment ability of market volatility-timing and joint market timing; the idiosyncratic risk at the individual trust level.
This thesis uses daily data to capture intermittent timing behavior and employs GARCH-type models to address the econometric problems of autocorrelation and heteroscedasticity owing to the employment of daily returns. This thesis documents how trust managers can time the market volatility successfully, whereas this is less the case with how they time the market returns. Moreover, data frequency cannot explain the empirical findings of reverse return-timing behavior. Volatility-timing evaluation is sensitive to data frequency, indicated by the opposite results obtained from daily and monthly data analysis.
Trust managers select stocks to construct their portfolios. Stock’s idiosyncratic risk related to firm news and unpriced by market returns deserve as much attention as market risk. Our last study concentrates on the idiosyncratic risk of unit trusts’ portfolio that highly depends on trust managers stock-picking decisions. The study breaks down each trust’s total idiosyncratic risk into aggregate idiosyncratic risk capturing typical responses of trust managers to the public firm news and trust-specific unique risk assessing the risk-taking decision of each unit trust manager.
We emphasise the relationship between realized returns of the unit trust and its unique risk exploring whether trust managers can produce high returns for trust investors when they take relatively high additional risk comparing to peers. The finding of significant positive relationship in the short-term across all trusts is favourable, supporting that managers are rewarded for their aggressive investment. Our finding can advise trust investors to invest in unit trusts with relatively high risk within their risk tolerance and capability. The positive relationship, nevertheless, is not consistent; thus, it is essential for investors to timely switch unit trusts timely
Exploring the Use of Plant Volatiles as a Sustainable Control Method for Glasshouse Whiteflies on Glasshouse-Grown Tomato
Get PDFPh. D. ThesisIn the UK, tomato (Solanum lycopersicum L.) is cultivated in bespoke glasshouse systems which facilitate the use of sustainable pest control techniques such as integrated pest management (IPM). IPM focuses on the use of naturally occurring control agents and is globally endorsed as the future paradigm for crop protection. Despite this, important tomato pests such as glasshouse whiteflies (Trialeurodes vaporariorum Westwood) are often still managed with insecticides. These synthetic chemical sprays, to which whiteflies have shown resistance, are extremely detrimental to the environment and human health. Plant volatile organic compounds (VOCs) offer an environmentally benign alternative to insecticides and have great potential for incorporation into IPM systems. This thesis explored the use of VOCs to control glasshouse whiteflies on tomato in a commercial glasshouse setting.
In a series of intercropping experiments with whitefly non-host plants, we found French marigold to effectively ‘push’ whiteflies from a tomato crop through emission of airborne limonene. We then used repellent limonene dispensers in place of companion plants, and also in conjunction with methyl salicylate, a potent inducer of plant defence. This combined VOC-based protection method performed no better than the standalone limonene treatment, meaning there was no synergy between the two compounds. These experiments highlighted the defensive inadequacies of cultivated tomato and prompted us to analyze whitefly resistance mechanisms in Solanum pimpenillefolium, a wild tomato species more resistant to whiteflies. Superior defences in S. pimpenillefolium were characterized by greater quantity and diversity of VOC emissions than cultivated tomato. In olfactory preference experiments, S. pimpenillefolium VOCs were less preferred by whiteflies and more attractive to the whitefly parasitoid Encarsia formosa. Host plant resistance is a key component of IPM and these results illustrate the importance of tomato VOCs for whitefly resistance. The methods and concepts explored in this thesis could be used to support current IPM systems and help achieve sustainable whitefly control.Stockbridge Technology Centre, Biotechnology and Biological Sciences Research Council (BBSRC
Identification of MYC-dependent therapeutic vulnerabilities for targeting Group 3 medulloblastoma
Get PDFPh. D. ThesisIntroduction
Group 3 medulloblastoma (MBGroup3) is a highly aggressive tumour characterised by MYC amplification and elevated expression (17% of MBGroup3). MYC amplification confers a dismal prognosis, and there is an urgent unmet need for novel therapeutic approaches. The identification and targeting of MYC’s biological dependencies thus represent a promising strategy to treat MYC-driven MBGroup3 tumours.
Methods
Three independent MYC-regulable isogenic MBGroup3 cell lines, in which MYC expression can be directly regulated by shRNA, were used to characterise MYC-dependency in these novel models of MBGroup3 tumours. The lines were used to investigate the role of MYC in drug resistance and sensitivity by characterising the MYC-dependent response to a panel of cancer therapeutics and small molecule inhibitors, to identify drugs whose efficacy is MYC-dependent, or which synergise with MYC knockdown. Three indirect MYC-targeting strategies (targeting MYC transcription and MYC mRNA translation) were assessed using candidate drugs, alongside undertaking a high-throughput compound screen (HTCS) (>500 inhibitors) using the models.
Results
Data from the MYC-dependent lines was used to identify MYC-dependent differences in drug-sensitivity between MYC-overexpressing and MYC-knockdown cell lines after inhibition of specific proteins. This approach identified several specific druggable dependencies (e.g. cell cycle regulators, DNA-damage response controllers, mitotic control machinery) with potential for the development of treatments against MBGroup3. Integration of drug-sensitivity results with data on MYC transcriptional (by RNA-seq) and biological (by whole-genome CRISPR screening) dependencies in the models, identified BRD4, PLK1, CHK1 and AURK as specific molecular targets. Subsequent validation of target inhibition revealed MYC-dependent effects, associated with downregulation of MYC and target-dependent pathways, across MBGroup3 models.
Conclusions
These findings support the development of PLK1, CHK and AURK inhibition as therapeutic approaches against MYC-dependent MBGroup3. Future work is now essential to validate our findings in vivo, to support the design of future clinical trials
The interaction profile between CDC20 and the components of the anaphase promoting complex or cyclosome (APC/C) in human Hela cells
Get PDFPh. D. ThesisThe mis-segregation of chromosomes during mitosis can lead to genetic disorders,
like Down syndrome, birth defects and even cancers (5-9). The spindle assembly checkpoint
(SAC) is the most important mechanism in mitosis (3, 10). The SAC functions to prevent
premature sister-chromatid segregation - at anaphase onset by inhibiting the premature
activation of the anaphase promoting complex/cyclosome (APC/C) by its coactivator CDC20
(cell division cycle protein 20) (10, 12). The APC/C is a large multi-subunit protein complex
which functions as an E3 ubiquitin ligase and targets substrates by ubiquitination and
consequently destruction by the proteasome throughout the cell cycle (reviewed in 61). It
contains three functional subdomains: the scaffolding platform consists of APC1, APC4, and
APC5; the catalytic domain consists of APC2 (a Cullin family related protein), APC10 (Doc1)
and APC11 (RING finger protein); and the TPR (tetratricopeptide repeat) lobe domain
consists of APC3, APC6, APC7, APC8, APC13, APC16 and Cdc26 (Reviewed in 63). The
spatiotemporal activation of the APC/C is primarily achieved by sequential and regulated
binding to its two co-activators, CDC20 and Cdh1 leading to the formation of APC/CCDC20 and
APC/CCdh1 which are two E3 ligase complexes (Reviewed in 61). The APC/CCDC20 primarily
controls the metaphase/anaphase transition and mitotic exit by targeting and destroying
Cyclin B1 and securin through regulation by the SAC (Reviewed in 61). More recently, it has
been shown that the APC/C can interact with a second CDC20 and target other substrates,
such as Nek2A and Cyclin A which are degraded in prometaphase independently of the SAC
(64). As the interaction between CDC20 and the APC/C, or the CDC20MCC and the APC/C has
never been seen in vivo, it will be important to understand the timing of these interactions
and the part that they play in regulating the APC/C (50, 52). Therefore, the overall aim of
this project is using PLA to investigate the protein-protein interactions between the
components of the APC/C and its co-activator, CDC20; and the interactions among the
subunits of the APC/C to provide insights into the regulation of the APC/C. We have studied
the in vivo protein-protein interactions between APC3-CDC20, APC8-CDC20, and APC11-
CDC20 and intended to examine the interactions between CDC20 and the APC/C. We have
also examined the dynamic assembly of the APC/C by looking at APC3-APC6, and APC3-
APC10 complexes. Our results suggest that APC11-CDC20APC8, and APC11-CDC20APC3
interacted at the same time, and we favour the interpretation that there is only one APC/C.
The interaction profiles of the APC3-APC6 and APC3-APC10 suggest that the assembly of the
APC/C is cell cycle regulated
The enchantment of the wild a journey into wildness through listening
Get PDFPh. D. Thesis.This research originates in three interrelated themes: the detachment from nature, the disenchantment
of the world and the ocularcentrism of our culture.
With regards to detachment from nature, we live in paradoxical times: on the one hand, we are
deeply entangled with nature by the resources that sustain us and through scientific and technological
developments, and on the other hand, we still hold onto an idea of nature as pristine wilderness
that we seek to protect and escape to. This bifurcated meaning of nature implicitly conveys an
instrumental view of nature and a residual rationalist tradition where the rational human is regarded
as superior to the non-human.
In parallel to the detachment from nature that intensified during the scientific revolution and onset of
capitalism at the end of the Renaissance period, the world underwent progressive disenchantment,
as everything was knowable through reason. The primacy of rational thought is therefore at the
heart of detachment from nature and the disenchantment of our lives and is heightened by modern
ocularcentrism that facilitates our abstraction from the world.
In this research, I propose that our detachment from nature does not stem from a lack of access
to it, but rather, from a set of cultural values that prevent us from engaging with the wildness that
we live entangled with. I aim to cultivate moments of enchantment with the wild as a vehicle to
reconnect with nature and expand beyond its rational apprehension. To that end, I connect to the
literal meaning of enchantment as mesmerizing through chants or sound and work with listening
as a creative research method. Aim and method are developed into two strands that are carried
out throughout the research and developed through the four initial chapters of this work: journey to
enchantment, and enchantment and beyond.
In Journey to Enchantment, wildness and enchantment are sought in a spontaneous urban wildness
and a remote wildness. Through the methodology of the soundwalk, walking whilst listening
attentively, I develop a deep engagement with the environment that gives rise to several temporary
installations and a practical guide to sound for landscape architects.
In Enchantment and Beyond, I revisit key moments of enchantment to develop a phenomenology
of enchantment that builds on Merleau-Ponty’s notions of flesh and wild being. Enchantment, I
propose, unveils a connection with the environment that exposes an inner wildness: uncontrollable
moments of extreme sensing where the experiences of time and individual self are suspended in
favour of a sense of anonymity and correspondence with one’s surroundings.
I conclude that the wild that we have lost a connection with is within us, and that sound can be
a vehicle for reaching it. Drawing on key components of Val Plumwood’s ecological self and
Jane Bennett’s vital materialism I argue that the power of the wild being stems from exposing our
commonality with the others. Coming out of enchantment, coming into our personal and rational
selves, we develop a care for the other that stems from having sensed our common essence that
enables us to shape our values and actions accordingly.Newcastle Institute for Creative Arts Practice
Exploring the role of sociotechnical systems to support deliberative localist decision-making
Get PDFPh. D. ThesisThe importance of civil society to our communities has always been socially significant but has an
increasingly important economic and democratic function. The localism agenda of successive
governments has pushed local authorities to devolve powers and responsibilities for community-level
policymaking to civil society organisations while, at the same time, significantly reducing the funding
required to adequately support such processes. Civil society groups are expected to fill the gaps left by
local authorities without the skills, resources and experiences, or without the bureaucratic processes
or participatory models of their erstwhile incumbents. At the same time, a crisis in democracy caused
a growing mistrust of the political class has raised questions about the legitimacy of our political
systems, and the aggregative logic of the internet, fuelled by nefarious politically motivated actors,
has further obfuscated the boundaries between truth and knowledge. The thesis put forward in this
dissertation is that in order for civil society to cope with the increased responsibilities that have been
devolved to it while maintaining their civic and democratic duty, new and more extensive
participatory forms of public engagement, and the sociotechnical systems to support such processes,
are required—first, to foster inclusion and second, to realise the ethical, epistemic, democratic and
civic virtues fostered through public deliberation about issues of shared concern.
Deliberative systems—the idea of a distributed talk-based model of democracy—forms the
underlying theory that drives this research, both conceptually in the way it motivates design and
practically in the ways in which it shares the participatory ideals of localism. This dissertation seeks to
explore the use of sociotechnical digital artefacts (or, sociodigital artefacts) to investigate the ways in
which deliberative democracy is enacted in instances of localism where ‘highly interested’ but ‘nonrepresentative’ actors are collaboratively carrying out policy-making activities, taking decisions that
affect the lives of their communities. This exploration takes shape over three case studies where I
design, deploy, and evaluate the role of a sociodigital system intended to foster the qualities of
deliberative democracy. In the final chapters I synthesise the insights from each study around a
discussion on the interrelationship between HCI, localism, and deliberative democracy with a focus
on the role of technology to support devolved decision-making
The role of farming groups in improving the livelihoods of women smallholder farmers in Zanzibar
Get PDFPh. D. Thesis.Agriculture continues to be an important sector for the economic development of many SubSaharan African countries. In the region, agriculture is dominated by poor smallholder
subsistence farmers who face several challenges to improve their production. The majority of
these farmers are women who contribute substantially to food production and for the general
economy of their communities. These women face greater challenges in access to productive
resources compared to men due to the existing gender gap. Collective action in agriculture is
suggested to overcome challenges facing smallholder farmers, and many governments and
supporting organizations in the region prefer to work with various forms of farming groups
rather than individuals. The study aims to determine the role of farming groups in livelihood
improvement of rural smallholder women farmers in Zanzibar, a part of the United Republic
of Tanzania.
Through the use of mixed methods whereas qualitative methods were the major, the study used
the Social Relation Analysis approach to determine the role of supporting organizations to
improve the abilities of women for better implementation of their group’s activities towards
better livelihood outcomes. Qualitative data were collected in 2017, and quantitative data in
2018 for the ability to generalization. In-depth interviews were conducted to key informant and
women farmers in four districts followed by a face to face questionnaire with women. Insights
demonstrate that through groups, women have increased their knowledge and application of
improved farming methods which contributes to their increased production and improved
livelihood. Through collective action women have increased their access to agricultural
resources, and have improved their social capital, hence women have experienced social and
economic empowerment. However, groups have demonstrated different achievements due to
the different abilities of members in a particular group. The study urges the supporting
organization to provide special support in favour for women to improve their abilities for better
achievement of their livelihood outcomes.Sultanate of Oman
under the Oman Academic Fellowshi
Process development for the continuous epoxidation of renewable terpenes using “Mesoscale” 3D-printed oscillatory baffled reactor
Get PDFPh. D. Thesis.A continuous process was developed for the epoxidation of (R)-(+)-limonene and α-pinene with
an oxidant (H2O2) using a polytungstophosphate catalyst in a mesoscale Oscillatory Baffled
Reactor (mesoOBR). Waste biomass derived (R)-(+)-limonene and α-pinene were used as an
alternative to petrochemical-based epoxides. A selective process towards the epoxides was
investigated by the screening of process parameters including temperature, oxidant molar ratio,
sodium sulphate (Na2SO4) amount, acid (H2SO4) concentration and solvent type. The mass and
heat transfer limitation associated with the exothermic and biphasic epoxidation reaction was
overcome using new 3D-printed baffles in the mesoOBR platform.
Screening the process parameters for the epoxidation of (R)-(+)-limonene revealed that a high
H2O2 conversion (~95 %) and selectivity to the limonene-1,2-epoxide (100 %), was able to
achieve in 15 minutes with a single-step addition of H2O2. The operating conditions included a
50 °C temperature in an organic solvent-free environment, with a (R)-(+)-
limonene/H2O2/catalyst molar ratio of 4:1:0.005. To prevent the hydrolysis of the epoxide, the
reaction mixture was saturated with Na2SO4 (5.7 g). An acid concentration of lower than 0.04
M was used and found to have a significant effect on the selectivity. Kinetic studies were
performed to allow modelling of the reaction scheme. A kinetic investigation showed that the
reaction was first-order in terms of (R)-(+)-limonene and catalyst concentration, and fractional
order (~0.5) with respect to the H2O2 concentration. The activation energy for the formation of
limonene-1,2-epoxide and limonene1,2-diol was determined to be ~36 and 79 kJ mol‒1
,
respectively.
The epoxidation of α-pinene with H2O2 was also performed using polytungstophosphate
catalyst. The variables in the screening parameters were temperatures (30–70 °C), oxidant
amount (100-200 mol%), acid concentrations (0.02-0.09 M) and solvent types (1,2-
dichloroethane, toluene, p-cymene, and acetonitrile). Screening the process parameters revealed
that a 100% selective epoxidation of α-pinene to α-pinene oxide was possible with negligible
side-product formation within a short reaction time (~20 minutes), using process conditions of
a 50 °C temperature in an organic solvent-free environment and a α-pinene/H2O2/catalyst molar
ratio of 5:1:0.01. A kinetic investigation also showed that the reaction was first-order in terms
of α-pinene and catalyst concentration, and fractional order (~0.5) with respect to the H2O2
concentration. The activation energy of ~35 kJ mol-1 was obtained for the epoxidation of αpinene, which was similar to ~36 kJ mol-1 for (R)-(+)-limonene.
Novel 3D-printed orifice baffles were integrated with a mesoscale oscillatory baffled reactor
for the continuous epoxidation of terpenes ((R)-(+)-limonene and α-pinene) with H2O2 in an
organic solvent-free environment. The biphasic reaction is highly exothermic, usually requiring
solvent, tight temperature control and effective multiphase mixing. The performance of the new
3D-printed single, tri- and multi-orifice baffles was compared to conventional helical and
integral baffles. The performance investigated were the mixing intensity, induction period,
multi steady state and heat removal capability. Passive isothermalisation was also investigated
using mesoOBR in a heat pipe assembly. The tri- and multi-orifice baffles were able to
overcome mixing limitation in continuous epoxidation and achieved a comparable rate of
reaction to batch epoxidation at mixing condition of oscillatory Reynolds number (Reo) >850
and Reo >500, respectively. Both baffles exhibited rapid steady state attainment, shorter
induction period at t = 1.5 residence time (τ) and better reproducibility with product variation
of ~ 1.3%. Other mesoOBRs designs had induction times of 2.0 τ – 3.0 τ and product variations
in the range of 1.6 – 2.1 %. The helically baffled mesoOBR designs demonstrated effective heat
transfer capability, allowing the reaction to being operated isothermally with ±1 °C temperature
variation in an organic solvent-free condition. Thisremoves the need of a solvent, thus reducing
reaction volume by a 5-fold. The timescale for the reaction was reduced from ~ 8 hours in a
conventional process to 30 minutes in the multi-orifice mesoOBR, a 16-fold reduction.
Therefore, a better process has been developed for a continuous epoxidation of (R)-(+)-
limonene and α-pinene with H2O2 using multi-orifice mesoOBRs, with a potential
intensification factor of ~ 80.Universiti Putra Malaysia,
The Ministry of Education, Malaysia, Engineering and Physical Sciences Research
Council (ESPRC
Earnings Management, Earnings Benchmarks, and Directors’ Remuneration: UK evidence
Get PDFPh.D ThesisThe primary objective of this study is to examine the quality of earnings reported by UK markets and explore whether firms manipulate reported earnings figures to hit specific targets. The analysis commenced by detecting earnings management using accrual-based earnings management and real activities manipulation. On the one hand, this study has aimed to investigate whether firms manage reported earnings by utilising accrual-based and real earnings management that just meet or beat important earnings benchmarks around zero earnings and last year’s earnings. On the other hand, this study purposed to examine the relationship between directors’ remuneration and their earnings management as to whether firm directors gain an excessive level of remuneration through managing reported earnings.
Using accounting and financial data from firms in the FTSE All-share between 2009 and 2015, the first part of this thesis revealed that UK firms are more likely to engage in real activities manipulation through reducing discretionary expenses and overproducing to manage earnings upwards when just meeting the zero level of earnings benchmark. Moreover, it has been established that firms in the UK market are not engaging in managing earnings upwards by utilising real activities manipulation via sales-based manipulation and overproduction, but are involved more in real activities manipulation by reducing or cutting discretionary expenses when just meeting the previous year’s earnings benchmark. In addition, this study undertook an additional analysis ascertain that UK firms with negative earnings have incentives to use accrual-based earnings management and real activities manipulation through managing discretionary expenses and manipulating production costs to manage earnings downward.
The second part of this thesis built a new model to measure abnormal directors’ remuneration and to indicate the degree of an excessive level of compensation gained by directors. Evidence was found that, UK directors report a decline in performance by using sales-based manipulation to manage earnings downward in order to receive additional rewards, whilst directors use production costs-based manipulation to boost earnings. The results also reveal that UK directors engage more in accrual-based earnings management to manipulate earnings downward to achieve abnormally high compensation themselves. Therefore, these results show that firms engage in accrual-based earnings management and real activities manipulation to manage earnings upwards or downwards to hit different specific targets.
The thesis presented a more comprehensive understanding of earnings management for the UK market, and offered forward some practical implications for researchers, policy makers, standard setters, and other practitioners. For example, it implies that there is higher demand for increased scrutiny or constraints regarding accounting discretions to eliminate earnings management and to ensure firms disclose good quality earnings information to the public; it draws the attention of regulators or standard-setters to the limitations of accounting regulations and standards and encourages them to implement improvements; the necessity for a closer scrutiny by auditors and regulators is suggested whilst, this thesis may motivate the Board to improve remuneration package setting to ensure directors act in the best interests of shareholders