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Stress-induced transcription factors and their role in RNA disruption in ovarian cancer cells
Get PDFWhen cancer patients respond positively to chemotherapy treatment, their tumour
ribosomal RNA (rRNA) is degraded, which has been termed RNA Disruption. The RNA
disruption assay (RDA) has been developed to quantify RNA disruption as an RNA disruption
index (RDI), which is the mass ratio of degraded to intact rRNAs. The underlying mechanism(s)
for RNA disruption remain unclear. RNA disruption occurs in vivo and in vitro in response to
various cellular stressors, including many structurally and mechanistically distinct chemotherapy
drugs. Therefore, there must be a common pathway or mechanism occurring in each of these
cases. Transcription factors are good upstream targets to begin elucidating a potential pathway or
mechanism for RNA disruption, since they are major regulators of gene expression. The goal of
this study was to: (i) identify transcription factors that are activated in response to treatment with
agents known to induce RNA disruption, (ii) create enriched cytoplasmic and nuclear extracts
from treated and untreated A2780 ovarian tumour cells, (iii) assess the relationship between
stress-induced RNA disruption and activation/altered localization of stress-induced transcription
factors in relation to RNA disruption. A2780 cells were treated with docetaxel or left untreated
as a control for 8 hours, and nuclear extracts from these cells were prepared. The activation of a
wide variety of known transcription factors in these extracts were analyzed using transcription
factor activation profiling plate arrays. The activation was measured based on their ability to
bind specific DNA sequences resulting in luminescence. Using a variety of criteria ranging from
statistical significance to relevance to stress in the literature, a few transcription factors of
interest were chosen: TFEB, TFE3, Nrf2, and YY1. Cytoplasmic and nuclear extracts were then
made from A2780 cells after treatment with doxorubicin, docetaxel, thapsigargin, and starvation
for 0, 2, 16, or 24 hours. The amount of RNA disruption was then assessed by RDA 72 hours
after treatment with the same stressors. Treatment with doxorubicin, docetaxel, thapsigargin, and
starvation resulted in significant change in RDI compared to control cells. Nrf2 was found
localized in the nucleus with or without treatment. Thus, Nrf2 appeared to be constitutively
activated in A2780 ovarian cancer cells, perhaps due to its role in cell survival. This study
corroborates the results of another study (Investigating the Relationship Between the Activation
of Transcription Factor Nrf-2 and Ribosomal RNA Degradation Upon Exposure to Various
Cellular Stressors, Carly Zulich, 2020) and eliminates Nrf2 as a potential transcription factor
associated with the activation of RNA disruption. Contrary to expected findings, there appear to
be higher levels of TFEB and TFE3 in both the cytoplasm and nucleus of the untreated and
DMSO vehicle control than cells treated with chemotherapy or other cellular stressors. Future
studies could investigate the potential of other transcription factors as targets for elucidating the
mechanism(s) for RNA disruption
Geological, fluid-chemical and petrochronological studies of the East Kemptville Sn(-Cu-Zn-Ag-In) deposit and its Devonian host batholith (Nova Scotia, Canada).
No full textPrimary tin ores form in magmatic-hydrothermal systems related to highly-evolved granites
enriched in lithophile elements (e.g., Li, Cs, Rb, U). Causative magmas are sourced from melting
(or contamination by) enriched crust, or from melting hydrothermally-altered mantle. These
granites form in large, multi-phase complexes (batholiths) and concentrate tin through fractional
crystallization. The latter increases volatiles (H2O, F) in residual melts that are emplaced at
shallow crustal depths, and thus the hydrothermal component to Sn-systems. Volatiles exsolve
into aqueous fluids that contain soluble Sn2+. These fluids typically separate into highly-saline
brines and vapours, and precipitate ore (SnO2) via oxidation of the Sn2+
. The fluids focus along
fractures in the crust and their accumulation is dependent on fluid- versus lithostatic pressures. The northern Appalachian evolution included incremental emplacement of numerous batholiths
and tin occurrences. The largest of these is the South Mountain Batholith (SMB) in Nova Scotia,
which was emplaced deep in the crust; although is host to multiple evolved granites, the SMB
contains only one significant tin deposit at East Kemptville (EK). To establish the depositional
setting of EK at a greater crustal depth, this thesis analyses its geology and fluid chemistry as
well as stable (O) and radiogenic (Re-Os, U-Pb, Lu-Hf) isotopes for both EK mineralization and
the zircon minerals that represent the SMB. The study addresses the absence of other significant
tin deposits in the SMB by evaluating the source of metal endowment.
Due to its deep emplacement, the fluids at EK show no evidence of phase separation, yet
abundant evidence of pressure-cycling. The latter allowed for replenishment of ore fluids during
deposit formation; whereas initial tin formed via fluid-rock exchange, later ores formed from mixing with foreign fluids. This segmented hydrothermal evolution at EK is reflected by a
range of mineralization ages.
The zircon ages and chemistry indicate: 1) the SMB formed over 15-20 m.y. from altered mantle
melts that underwent contamination by host rocks; and 2) the EK host is temporally and
isotopically distinct from the SMB, and likely evolved from a lower crust-derived melt. The
distinct source suggests other tin occurrences in the region share a similar origin
Putting the village back into the urban village: recovering a new commons for Gui Yang, Chengguan Village, China through adaptive re-use and landscape recovery
No full textThe aim of this project is to discover and probe the challenges that exist in
Chengguan Urban Village through interviews and mapping, after initial field
work and site reconaissance, I will apply architectural interventions, such as
spatial and functional aspects to adress thesis issues and challenges. -Historical interpretive research is the method I used in the research process
of this project. Through the study of the historical development of Chengguan
Village I will attemp to understand the changes in the lives of the villagers.
The Guizhou Aluminium Factory opened a branch in Chengguan Village
in 1950, and Chengguan Village has since become a village dominated by
both industry and agriculture. Until around 2000, the aluminum plant was
abandoned and the villagers' agricultural land was completely expropriated
by the government. With the development of more formal cities by the
Chinese government, the gap between urban villages and city life is getting
wider and wider. The living demands of the villagers have also changed, and
more facilities and services should follow suit, such as recreational facilities,
garbage sorting facilities, daycare, medical facilities, and agricultural
production conditions. -Precedent studies is a way to make investigations more in-depth. After
the problem is found, the design strategy of other projects will serve as an
effective reference and thinking. I will analyze the key projects designed by
Urbanus and Turenscape, to inject new elements and meanings into my
project, such as adding new materials to old buildings to create a different
atmosphere, and how to transform old buildings to give them new functions.
I will distill the lessons learned from these, and add these to my own design
project. - Field Work and Site Reconaissance, I have both identified, as well as distill
and analyze several challenge and needs which includes the phenomenon of
the wet market, garbage challenge and the demand for agricultural land. Wet
market is built on the first floor of a residential building, which shares the
indoor parking space and outdoor space with the residents. The main
challenge of these wet market is hygiene, with residents unable to tolerate
the smell of vegetable leaves, chicken feathers, and fish scales which the
vendors throw away every day. In addition to the inconvenience of living,
poor sanitation poses some health risks to households, traders and villagers
- it could even cause massive disease. The problem of waste in the village
is also very serious. Although there are several trash bins in the village, the
villagers still throw away their garbage at will. There is also a conscious lack
of garbage classification and lack of facilities. For these problems, I propose
to establish a multi-functional new commons for the establishment of new
markets waste management, and even more service and entertainment
space. This will form the new self-organized economy for the villagers,
which is designed to improve the quality of life of villagers and make them
financially self-sufficient
Deep learning models for survival analysis on histology images
No full textIn this study, Histology images of the patients were used as input to the Convolutional Neural
Network (CNN) models to predict the risk of the patients with brain tumour. Motivation for
this study was to highlight the emerging role of deep learning in the field of precision
medicine and suggest an expanding utility for computational analysis of histology in the
future practice of pathology. The Region of Interest (ROI) of the histology images
(1024x1024 pixels) of brain tumour of 769 patients was used to build a machine learning
model which can predict the hazard ratio (is frequently interpreted as risk ratio) of the
patients and survival time of the patient. Five diverse CNN models have been trained namely,
DensNet121, VGG-19, Xception, Inception-V3 and Inception-ResNet-V2. The loss function
of Cox-proportional hazard has been used to fit a survival model. For each CNN survival
model, a 15-fold cross validation was implemented on the training data. The image data for
769 patients was split into 80% as training with 616 patients and 20% for testing consisting
of 153 patients. There are 1239 ROI images for 616 patients and 266 ROI images of 153
patients. For each cross validation, the CNN model was trained for 100 epochs. For the test
data (153 patients), 9 High Power Fields (HPFs) (256x256 pixels) were sampled from each
ROI, and a risk is predicted for each field. The Median HPF risk is calculated in each ROI
and the second highest value among all ROIs was selected as the patient risk. The predicted
risk is calculated by taking the average of predicted risk for the last 5 epochs. The median
concordance index (CI) and integrated brier score (IBS) is evaluated from the predicted risk
and are compared for each of the models. Wilcoxon Ranksum test is used to test the null
hypothesis that the CI and IBS of five CNN models was significantly different for 5%
significance level. From the five CNN structures, DensNet121 had the best performance,
which was followed by VGG19, InceptionResNet-V2, InceptionV3 and Xception,
respectively
Culture of wilderness retreat in the Algoma region: decompostable architecture along the Agawa River
No full textThe Candian Wilderness has the potential
to create social, mental, spiritual and
physical advantages within modern
culture. The study of these advantages
associated with the context of the
Wilderness and the city has led to a
proposal that explores the habitable space
in between. This thesis proposes a better
balance between the Wilderness and
the City. With the creation of a retreat; a
place to escape the city and live simply in
the landscape. Inhabiting the Wilderness
without the distractions of technological
communication will allow the inhabitants
to “enjoy the freedom from the grip of
the external world,”
1
a necessary step to
better establish a relationship with the
landscape. The Retreat is a place that is
situated deep in the Wilderness in order
to gain the benefits from its context until
the inhabitant’s eventual return to the city.
Programmatic characters are meshed
together informing habitation, form,
material and construction. Creating a
space that is directly shaped by the flora
and topography and satisfies the essential
elements of survival. Camps or in-between
spaces are part of Canadian culture and
act as a resource for rest, creation and
exploration, rather than a resource for
economic growth. This change can be
seen in the Algoma region of Ontario
w here infrastructure built for resource
extraction and transportation has been
transformed to include opportunities for
Wilderness exploration, interpretation and
escape. Communities of people living and
working in the Wilderness of Algoma as well as Canadian artists have created
spaces in between for themselves,
in doing so, they created a culture of
Wilderness habitation.
The Agawa Retreat is an exploration in
Wilderness habitation. Situated along the
Agawa River the Agawa Retreat acts as
a prototype where human occupants and
the Wilderness interact on a personal level.
This is achieved with the use of modern
mapping and modeling techniques and a
unique approach to material selection. The
Wilderness acts as both the site context
and occupant, resulting in an approach
to a building life-cycle that considers
habitation one phase of decomposition
and renewal. The Agawa Retreat is a
unique building typology that is adaptable
and repeatable in almost any Wilderness
setting. Its site placement, material
choice and construction procedure all
consider the Wilderness as a character
that inhabits the proposal alongside and
human occupants. Doing so creates a
space in between the Wilderness and
the city where occupants can escape,
create and live simply surrounded by the
Canadian landscap
Cellular effects of Ferula Assafoetida on breast cancer cells and inflammatory responses in cultured monocytes
No full textIn traditional medicine, Ferula assafoetida (F. assafoetida), has been used as an antiseptic,
anti-diabetic, anti-inflammatory, and anti-cancer agent. In recent years its anti-cancer and antiinflammatory activities have become a focus in drug research. We investigated the in vitro
cytotoxicity and anti-inflammatory effects of ethanolic extracts of F. assafoetida and five known
components (ferulic acid, vanillic acid, quercetin, ellagic acid, and p-coumaric acid) on a group of
malignant and non-malignant breast cell lines and the THP-1 monocyte-like cell line. Our results
showed that treatment with the ethanolic extract of F. assafoetida, and the components, had a
significant effect on cell viability and apoptosis induction for the human MCF-7, MDA-MB-231,
and murine 4T1 breast cancer cell lines compared to the non-malignant human HBL-100 breast
cells. This research also showed that THP-1 peripheral blood monocytic leukemia cells,
differentiated into macrophages, could be further polarized into the M1 inflammatory phenotype
by treatment with extracts of F. assafoetida and the components. There was a significant increase
in the expression of CD80, a marker associated with the M1 macrophage subtype, but no increase
in expression of the M2 subtype marker, CD163, in treated cells. Further, this polarization of the
THP-1-dependent macrophages showed an increased ability to damage MCF-7 or MDA-MB-231
cell monolayers in co-culture experiments. Therefore, treatment with F. assafoetida extracts can
also indirectly cause the death of cancer cells via activation of immune cells. These results confirm
that F. assafoetida is a potential source of anti-cancer and immune modulatory compounds and
that further investigation is needed to reveal the mechanisms of F. assafoetida’s effects on
apoptosis and immunomodulation.Doctor of Philosophy (PhD) in Biomolecular Science
The perceptions of women in Northern Ontario about their reproductive healthcare
No full textWith a goal to improve service provision, this study examined the experiences of women
in Northern Ontario with respect to their uptake of reproductive healthcare services. As part of
my mixed methods study, women in Northern Ontario completed a survey, offered in English
and French, about their reproductive healthcare experiences, and a portion of participants were
also interviewed. A multimodal recruitment strategy and maximum variation sampling was
applied, with a goal of collecting the experiences of a diverse group of women.
Analysis was based on 173 completed surveys and 19 semi-structured qualitative
interviews. The interview data is grouped under five conceptual constructs, with “gender” as an
overarching construct, found to be a factor in the remaining four: the characteristics of good care;
the relationship with the provider; the care environment, and administrative practices.
Additionally, respondents felt that midwives excelled at providing quality reproductive
healthcare and would favour increased access to midwives for reproductive health care
throughout their lives.
For the survey data, I used descriptive statistics and multivariate linear regression models
to determine whether residency, language, education, income, overall health, access to care,
having a family physician, and preferring female providers (independent variables) were
associated with the perceived quality of reproductive healthcare services and choosing a
midwife. Most survey participants rated their reproductive healthcare experiences as fair to good
overall but indicate room for improvement in the relationships with their providers and
administrative support. Women residing rurally, without a family physician, and lower
socioeconomic status are statistically more likely to prefer a midwife for reproductive healthcare. The survey results indicate a preference for female healthcare providers by the majority of
interviewees.
Changes driven by strong health policy may be required to engage women in
recommended reproductive healthcare more fully. Although northern geography will always
present challenges that may not be subject to amelioration, other factors preventing women from
accessing care are more amenable to change, and as argued here, this is a right of women and an
obligation on the part of governments to provide equitable access for all Canadians to healthcare
services
Predicting liver cancer on epigenomics data using machine learning
No full textEpigenomics is the branch of biology concerned with the phenotype modifications that do not
induce any change in the cell DNA sequence. The word Epigenomics is made of two-words, epi
and genomics; epi comes from the Greek prefix. Epi- in epigenomics implies features that are
"on top of" or "in addition to" the traditional genetic basis for inheritance. So, essentially to
modify the properties, it applies something to the top of DNA, which ultimately prevents such
DNA actions from being executed. These alterations arise in the cancer cells, which is the only
cause of cancer. In this research, the objective is to propose a solution for the identification of the
best genes of Liver Cancer from gene expression. Four different types of data are used in this
research to predict cancerous cells in LIHC (liver hepatocellular carcinoma) patients. The data
includes methylation, histone, the human genome, and RNA-Sequences. The data is accessed
through open-source technologies in R programming language. The data is processed to create
features, and with the help of statistical analysis and advanced machine learning techniques, the
prediction of liver cancer is obtained from the fine-tuned model.Master of Science (MSc) in Computational Science
Stack shack: a modular prefabricated alternative to affordable housing
No full textThis thesis explores how modular design and
prefabricated construction methods can sustainably
alleviate the affordable housing crisis in Dartmouth,
Nova Scotia. In particular, how the efficiencies
of these methodologies can be translated into a
less expensive dwelling for the owner, taking into
consideration the entire lifecycle of the building.
The proposal is effectively divided into two parts.
The first portion focuses on research, outreach, and
partnerships. Part two uses the findings to set the
parameters for a holistic design of a dwelling unit that is
versatile enough to be successful in a variety of contexts.
The area of Dartmouth affectionately known as
Between the Bridges is used as a case study for a
housing intervention. This somewhat marginalized
community of roughly 13,000 is a well established
residential neighbourhood that has access to
amenities and transit routes, and is ripe for the
addition of minimally disruptive hidden density.
With an average household income that is half of the
rest of Halifax, the thesis proposes that if a model
proves to be successful here, it could theoretically
be implemented and replicated in other housing
markets all over the country. In essence, the site is
considered an epicentre instead of a one-off proposal.
It is argued that a multi-pronged approach is
necessary, and that no single non-profit, institution,
or private developer can relieve the stresses that
people are feeling in the face of homelessness.
For that reason, this proposal sets out to develop a
unit that can be implemented through a variety of
organizations, in a multitude of contexts and scales,
and serves diverse and dynamic demographics.
Through strategic partnerships with non-profits,
various organizations, social enterprises, and
religious institutions, the aim is to secure funding
and identify potential personnel who could
benefit from the architectural proposal. The thesis
process acts as the “front end design” required to
develop a successful prefabricated housing unit
#BlackLivesMatter Movement and consequences of racism: a data and sentiment analysis on Tweets in the USA
No full textIntroduction: A movement arose in the middle of a challenging pandemic time. In a year that
everybody keeps their six feet distance and mask on, many came to the streets or started
publishing social media contents asking for Black rights. It was after an injustice killing of a
black man - George Floyd - by a police officer that #BlackLivesMatter trended again as the top
conversation in the world. Hence, it became our question that how racism - specifically on social
media - is associated with blacks' mattering lives.
Methods: We carried out an ecological retrospective study on Twitter data for the year 2020,
which had location tags inside the USA. We created inclusion criteria to shape our dataset based
on that and categorizing tweets into separate groups. Our groups were (1) "BLM" for those
supporting the "BlackLivesMatter" movement; (2) "Anti-BLM" containing tweets in opposition
to the first group; (3) "Ambiguous" who had both previous group contents; and (4) the "Racists"
comprising those who included offensive n-words in their tweets. We employed some statistical
data by utilizing previous research for the "Life Expectancy", "Poverty Rates," "Educational
Attainment," and "Race Compositions” factors of the black and white population in the USA by
the states. We employed additional techniques to identify genders and classify records in
reference to their states. Moreover, we applied the sentiment analysis using Python. We
calculated the final rates considering each group's statistics compared to the sum of all tweets
published in each state. The analysis of the final rates in correlation with employed tables was
done by IBM SPSS Statistics 26. Results: We found 43,830,301 tweets with location data inside the USA in this time frame, and
306,925 of them applied for our study. A noticeable initial observation was the sharp increase of
the #BlackLivesMatter after George Floyd's demise on May 25, 2020, while this hashtag has a
history back to 2013. There is a positive correlation between the rates of offensive-content
tweets and the life expectancy of Black males. The same tweets showed an association that
wherever racism is higher, more are suffering poverty. This is rather surprising that the
BlackLivesMatter movement supporters were mostly among those with the bachelor or advance
degree educational attainments. By contrast, if a state had lower rates of high school degrees,
more racists tweets exist there. The rates of aggressive tweets are higher in areas with more black
populations and are weaker in states having white people's domination. Regarding the sentiment
analysis, the majority of tweets are written in objective forms, and it had a slight increase after
the mentioned event. The polarities were also mostly in a neutral way. The most negative sense
belonged to the BLM supporters, with the rate of 46% before and 33% after the event.
Conclusion: This project was undertaken to evaluate the relationship between rates of cyberracism and anti-racism posts to some real-world indicators. We considered our inclusion criteria
in reference to the cruel killing of a black man – George Floyd - by police to investigate the
published tweets classified by supporters and opponents of this story, in addition to those using
offensive language towards black people. This study showed a strong correlation between these
concepts while contents on the world wide web could impute the day-to-day life conversation.
Hence, it shows how a drop in racist behaviors can lead to a world with higher life expectancy,
wealth, and education. Reduction of color discrimination on social media and particularly toward blacks could help to have a healthier community. Contrarily, the rise of these bigoted contents results in disastrous
consequences on these racialized populations.Master of Science (MSc) in Computational Science