Genetic architecture and sexual conflict in the life history of Drosophila

Because males and females of a species express many homologous traits, sex-specific selection on these traits can shift the opposite sex away from its phenotypic optimum. This mode of sexually antagonistic selection, known as intralocus sexual conflict (IaSC), arises when the evolution of sexual dimorphism is constrained by the two sexes sharing a common gene pool. As IaSC has been historically overlooked, many outstanding questions remain. For example, what is its contribution in maintaining genetic variation for fitness in populations? What characters underlie this variation in fitness? How does the selection history of the population influence the standing genetic variation? I used the model organism Drosophila melanogaster to attempt to resolve some of these questions. The first part of my Master’s project involved assessing the detectability of sexually antagonistic alleles in populations at different stages of adaptation to the laboratory. For the second part of my Master’s project, I looked for evidence of conflict during the development of body size, a well-known sexually dimorphic trait. While the first part of my thesis proved inconclusive, the second part revealed a surprising source of sexual conflict in pre-adult stages of D. melanogaster.

Genetic Polymorphisms in Replication-related Genes and Risk of Breast Cancer Among European and East Asian Women

Background: The role of common, low to intermediate risk alleles in breast cancer need to be examined due to their relatively high prevalence. Among many cellular pathways, replication has a pivotal role in cell division and frequently targeted during carcinogenesis. Replication is governed by a host of genes involved in a number of different pathways. This study investigates the effects of replication-gene variants in relation to breast cancer and how this relationship is affected by ethnicity, menopausal status and breast tumour subtype. Methods: Data from a case-control study with 997 incident breast cancer cases and 1,050 age frequency matched controls in Vancouver, British Columbia and Kingston, Ontario were used. Unconditional logistic regression was used to calculate odds ratios between 45 replication gene variants and breast cancer risk, assuming an additive genetic model adjusted for age and centre, presented for Europeans and East Asians separately. Polytomous logistic regression was used to assess odds ratios between each SNP and four breast cancer subtypes defined by hormone receptor status among Europeans. All analyses were stratified by menopausal status. The Benjamini–Hochberg false discovery rate (FDR) was used to address multiple comparisons. Results: Among Europeans, the SNPs in FGFR2, TOX3 and 11q13 loci were associated with breast cancer after controlling for multiple comparisons. Test of heterogeneity showed the SNPs rs1045185, rs4973768, rs672888, rs1219648, rs2420946 among Europeans and rs889312 among East Asians conferred differential risk across the tumour subtypes. Conclusions: Specific SNPs in replication genes were associated with breast cancer, and the risk level differed by tumour subtype defined by ER/PR/Her2 status and ethnicity.

The SHIVir Survey: A Dynamical Catalogue of Virgo Cluster Galaxies and their Scaling Relations

By virtue of its proximity and richness, the Virgo galaxy cluster is a perfect testing ground to expand our understanding of structure formation in the Universe. Here, we present a comprehensive dynamical catalogue based on 190 Virgo cluster galaxies (VCGs) in the "Spectroscopy and H-band Imaging of the Virgo cluster" (SHIVir) survey, including kinematics and dynamical masses. Spectroscopy collected over a multi-year campaign on 4-8m telescopes was joined with optical and near-infrared imaging to create a cosmologically-representative overview of parameter distributions and scaling relations describing galaxy evolution in a rich cluster environment. The use of long-slit spectroscopy has allowed the extraction and systematic analysis of resolved kinematic profiles: Halpha rotation curves for late-type galaxies (LTGs), and velocity dispersion profiles for early-type galaxies (ETGs). The latter are shown to span a wide range of profile shapes which correlate with structural, morphological, and photometric parameters. A study of the distributions of surface brightnesses and circular velocities for ETGs and LTGs considered separately show them all to be strongly bimodal, hinting at the existence of dynamically unstable modes where the baryon and dark matter fractions may be comparable within the inner regions of galaxies. Both our Tully-Fisher relation for LTGs and Fundamental Plane analysis for ETGs exhibit the smallest scatter when a velocity metric probing the galaxy at larger radii (where the baryonic fraction becomes sub-dominant) is used: rotational velocity measured in the outer disc at the 23.5 i-mag arcsec^{-2} level, and velocity dispersion measured within an aperture of 2 effective radii, respectively. Dynamical estimates for gas-poor and gas-rich VCGs are merged into a joint analysis of the stellar-to-total mass relation (STMR), stellar TFR, and Mass-Size relation. These relations are all found to contain strong bimodalities or dichotomies between the ETG and LTG samples, alluding to a "mixed scenario'' evolutionary sequence between morphological/dynamical classes that involves both quenching and dry mergers. The unmistakable differentiation between these two galaxy classes appears robust against different classification schemes, and supports the notion that they are driven by different evolutionary histories. Future observations using integral field spectroscopy and including lower-mass galaxies should solidify this hypothesis.

Software for Designing Custom Orbital-Craniofacial Implant Plans

Purpose: Custom cranio-orbital implants have been shown to achieve better performance than their hand-shaped counterparts by restoring skull anatomy more accurately and by reducing surgery time. Designing a custom implant involves reconstructing a model of the patient's skull using their computed tomography (CT) scan. The healthy side of the skull model, contralateral to the damaged region, can then be used to design an implant plan. Designing implants for areas of thin bone, such as the orbits, is challenging due to poor CT resolution of bone structures. This makes preoperative design time-intensive since thin bone structures in CT data must be manually segmented. The objective of this thesis was to research methods to accurately and efficiently design cranio-orbital implant plans, with a focus on the orbits, and to develop software that integrates these methods. Methods: The software consists of modules that use image and surface restoration approaches to enhance both the quality of CT data and the reconstructed model. It enables users to input CT data, and use tools to output a skull model with restored anatomy. The skull model can then be used to design the implant plan. The software was designed using 3D Slicer, an open-source medical visualization platform. It was tested on CT data from thirteen patients. Results: The average time it took to create a skull model with restored anatomy using our software was 0.33 hours ± 0.04 STD. In comparison, the design time of the manual segmentation method took between 3 and 6 hours. To assess the structural accuracy of the reconstructed models, CT data from the thirteen patients was used to compare the models created using our software with those using the manual method. When registering the skull models together, the difference between each set of skulls was found to be 0.4 mm ± 0.16 STD. Conclusions: We have developed a software to design custom cranio-orbital implant plans, with a focus on thin bone structures. The method described decreases design time, and is of similar accuracy to the manual method.

Quality Physical Activity Participation for Military Veterans with a Physical Disability

Minimal research has explored what comprises a quality physical activity (PA) participation experience, particularly among military Veterans with a physical disability for whom evidence of the benefits of PA is growing. To address this research gap, this dissertation examines quality PA participation among military Veterans with a physical disability. Manuscript 1 explores the views of Veterans with a physical disability regarding what elements constitute a quality PA experience, and how these elements may be fostered. Eighteen Veterans with various physical disabilities and PA experiences participated in interviews. Four quality elements were identified via thematic analysis: group cohesion, challenge, having a role, and independence and choice. A further three factors (the physical and social environments, and program structure) were identified as precursors for a quality experience. Manuscript 2 explores how PA programs for Veterans with a physical disability are delivered, and how these delivery strategies link conceptually to quality participation. Interviews were conducted with program staff from three PA programs for Veterans, and program documentation collected, to develop an understanding of program delivery strategies. Four strategies with potential links to quality participation were identified through thematic analysis: foster social connections, challenge participants, tailor programs and outcomes to match participant needs, and include knowledgeable coaches and instructors. Manuscript 3 evaluates the participation of Veterans with functional impairments in PA events, and examines the relationships among quality precursors, quality elements, and participation outcomes. Results indicate that program participation did not promote long-term increases in PA indicators. However, an indicator of the quality element belongingness mediated the relationship at particular time-points between coach interpersonal skills and three participation outcomes: family integration, PA intentions, and PA planning. These findings suggest that a quality participation experience created by coaches may positively impact the transition to civilian life, and promote efforts to engage in ongoing PA. Overall, this dissertation contributes towards a greater depth in understanding of the experiences of Veterans with a physical disability in PA programs. The findings begin to provide a foundation for researchers and practitioners aiming to create, deliver, and promote quality PA interventions and programming for Veterans with a physical disability.

Regulation of electrical transmission by protein kinase C in Aplysia bag cell neurons

Electrical synapses are composed of gap junctions, made from paired hemi-channels that allow for the transfer of current from one neuron to another. Gap junctions mediate electrical transmission in neurons, where they synchronize spiking and promote rapid transmission, thereby influencing the coordination, pattern, and frequency of firing. In the marine snail, Aplysia calfornica, two clusters of neuroendocrine bag cell neurons use electrical synapses to synchronize a 30-min burst of action potentials, known as the afterdischarge, which releases egg-laying hormone and induces reproduction. In culture, paired bag cell neurons present a junctional conductance that is non-rectifying and largely voltage-independent. During the afterdischarge, PKC is activated, which is known to increase voltage-gated Ca2+ current; yet, little is understood as to how this pathway impacts electrical transmission. The transfer of presynaptic spike-like waveforms (generated in voltage-clamp) to the postsynaptic cell (measured in current-clamp) was monitored with or without PKC activation. It was found that pretreatment with the PKC activator, phorbol-12-myristate-13-acetate (PMA), enhanced junctional conductance between bag cell neurons. Furthermore, in control, presynaptic action potential waveforms mainly evoked postsynaptic electrotonic potentials at both -60 and -40 mV. However, with PKC activation the presynaptic stimulus consistently elicited postsynaptic action potentials from resting potentials of -40 mV, and would occasionally result in firing from repetitive input at -60 mV. Moreover, to assess whether this enhanced electrical transmission genuinely reflects a greater junctional conductance or a change in postsynaptic responsiveness, a fast-phase junctional-like current was applied to single bag cell neurons. Neurons in PMA always fired action potentials in response to current injection as opposed to control, which were less likely to spike. This outcome did not change when the junctional-like current was artificially enhanced in control conditions. Also, in response to fast- and slow-phase electrotonic potential (ETP) waveforms, Ca2+ current was markedly larger in single PMA-treated neurons. These findings suggest that PKC activation may contribute to afterdischarge fidelity by recruiting postsynaptic Ca2+ current to promote synchronous network firing. Finally, Aplysia gap junction genes (innexins) were transfected into mouse N2A cells and characterized. This revealed a biophysical and pharmacological profile similar to native gap junctions.

FROM GENES TO GENOMES: LOCAL ADAPTATION AND ADAPTIVE POTENTIAL IN TWO ARCTIC SEABIRDS

By investigating the mechanisms underlying the evolution and the maintenance of local adaptations we can help predict how species will adapt to future environmental change. In this thesis I investigate local adaptation and adaptive potential in thick-billed and common murres (Uria lomvia and U. aalge), two arctic seabirds of international conservation concern. Thanks to the recent development of new genomic methods, I address three major themes that are relevant for both the development of evolutionary theory and conservation: 1) the role of gene flow in the origin and maintenance of adaptation; 2) levels and distribution of standing genetic variation, and their contribution to adaptive potential; and 3) the genomic mechanisms maintaining an adaptive dimorphism within a single interbreeding population. First, I review the literature on genomics of local adaptation with gene flow and find that adaptation can be maintained despite gene flow, that gene flow itself can promote adaptation, and that genetic architecture is important in the origin and maintenance of local adaptations. Second, I genotype genome-wide markers and toll-like receptor genes (TLRs) to investigate local adaptation and adaptive potential in thick-billed murres. Thick-billed murres do not show signatures of local adaptation to their breeding grounds, but outlier loci group birds according to their non-breeding distributions, suggesting that selection and/or demographic connectivity in the winter may explain patterns of differentiation in this species. Genetic variation at TLRs does not decrease with increasing latitude as predicted, but tests of selection and measures of genetic diversity suggest differences in local selective regimes at most genes. Thick-billed murres show high levels of standing genetic variation and their adaptive potential will mostly depend on rate and magnitude of environmental change. Finally, I improve and annotate the assembly of the highly heterozygous genome of the thick-billed murre. Using this assembly as a reference, I perform whole genome analyses to investigate the genomic basis of an adaptive dimorphism in Atlantic common murres. I show for the first time that a 60 kb complex copy number variant in a non-coding region maintains differences in plumage and cold adaptation despite high gene flow.

Landscape Patterns of Permafrost Disturbance and Degradation in the Canadian High Arctic

Intensification of permafrost disturbances such as active layer detachments (ALDs) and retrogressive thaw slumps (RTS) have been observed across the circumpolar Arctic. These features are indicators of unstable conditions stemming from recent climate warming and permafrost degradation. In order to understand the processes interacting to give rise to these features, a multidisciplinary approach is required; i.e., interactions between geomorphology, hydrology, vegetation and ground thermal conditions. The goal of this research is to detect and map permafrost disturbance, predict landscape controls over disturbance and determine approaches for monitoring disturbance, all with the goal of contributing to the mitigation of permafrost hazards. Permafrost disturbance inventories were created by applying semi-automatic change detection techniques to IKONOS satellite imagery collected at the Cape Bounty Arctic Watershed Observatory (CBAWO). These methods provide a means to estimate the spatial distribution of permafrost disturbances for a given area for use as an input in susceptibility modelling. Permafrost disturbance susceptibility models were then developed using generalized additive and generalized linear models (GAM, GLM) fitted to disturbed and undisturbed locations and relevant GIS-derived predictor variables (slope, potential solar radiation, elevation). These models successfully delineated areas across the landscape that were susceptible to disturbances locally and regionally when transferred to an independent validation location. Permafrost disturbance susceptibility models are a first-order assessment of landscape susceptibility and are promising for designing land management strategies for remote permafrost regions. Additionally, geomorphic patterns associated with higher susceptibility provide important knowledge about processes associated with the initiation of disturbances. Permafrost degradation was analyzed at the CBAWO using differential interferometric synthetic aperture radar (DInSAR). Active-layer dynamics were interpreted using inter-seasonal and intra-seasonal displacement measurements and highlight the importance of hydroclimatic factors on active layer change. Collectively, these research approaches contribute to permafrost monitoring and the assessment of landscape-scale vulnerability in order to develop permafrost disturbance mitigation strategies.

Cold acclimation of chill coma mechanisms in the locust CNS

Temperature has profound effects on the neural function and behaviour of insects. When exposed to low temperature, migratory locusts (Locusta migratoria) enter chill coma (neuromuscular paralysis) and can resume normal body functions after returning to normal temperature. Our laboratory has studied phenomena underlying environmental stress-induced comas in locusts and found that they are associated with a sudden loss of K+ homeostasis and also a temporary electrical silence in the central nervous system (CNS). However, the mechanisms underlying chill coma entry and recovery are not well understood, particularly the role of the CNS has not been determined. Here, I investigated neural function during chill coma in the locust by measuring electrical activity in the CNS. As pre-exposure to moderately low temperatures, either chronically (cold acclimation) or acutely (rapid cold hardening; RCH), has been found to improve the insect’s cold tolerance, I also determined cold acclimation and RCH protocols that will improve the locust's cold tolerance and whether these protocols affect neural shutdown during chill coma in the locust. With an implanted thermocouple in the thorax, I determined the temperature associated with a loss of responsiveness (CTmin) in intact male adult locusts. In parallel experiments, I recorded field potential (FP) in the metathoracic ganglion (MTG) in semi-intact preparations to determine the temperature that would induce neural shutdown. I found that acclimation at 10 ˚C and RCH at 4 ˚C reduced chill coma recovery time (CCRT) in intact animal preparations and RCH at 4 ˚C for 4 hours reduced the temperature at neural shutdown in semi-intact preparations. These results suggest that pre-exposure to cold can improve the locust's resistance to chill coma and support the notion that the CNS has a role in determining entry into and exit from chill coma in locusts.

ROLE OF THE FRONTAL EYE FIELD, SUPERIOR COLLICULUS, AND BASAL GANGLIA IN FLEXIBLE SACCADE BEHAVIOR

A distributed network of cortical and subcortical brain regions mediates the control of voluntary behavior, but it is unclear how this complex system may flexibly shift between different behavioral events. This thesis describes the neurophysiological changes in several key nuclei across the brain during flexible behavior, using saccadic eye movements in rhesus macaque monkeys. We examined five nuclei critical for saccade initiation and modulation: the frontal eye field (FEF) in the cerebral cortex, the subthalamic nucleus (STN), caudate nucleus (CD), and substantia nigra pars reticulata (SNr) in the basal ganglia (BG), and the superior colliculus (SC) in the midbrain. The first study tested whether a ‘threshold’ theory of how neuronal activity cues saccade initiation is consistent with the flexible control of behavior. The theory suggests there is a fixed level of FEF and SC neuronal activation at which saccades are initiated. Our results provide strong evidence against a fixed saccade threshold in either structure during flexible behavior, and indicate that threshold variability might depend on the level of inhibitory signals applied to the FEF or SC. The next two studies investigated the BG network as a likely candidate to modulate a saccade initiation mechanism, based on strong inhibitory output signals from the BG to the FEF and SC. We investigated the STN and CD (BG input), and the SNr (BG oculomotor output) to examine changes across the BG network. This revealed robust task-contingent shifts in BG signaling (Chapter 3), which uniquely impacted saccade initiation according to behavioral condition (Chapters 3 and 4). The thesis concludes with a published short review of the mechanistic effects of BG deep brain stimulation (Chapter 5), and a general discussion including proof of concept saccade behavioral changes in an MPTP-induced Parkinsonian model (Chapter 6). The studies presented here demonstrate that the conditions for saccade initiation by the FEF and SC vary according to behavioral condition, while simultaneously, large-scale task dependent shifts occur in BG signaling consistent with the observed modulation of FEF and SC activity. Taken together, these describe a mechanistic framework by which the cortico-BG loop may contribute to the flexible control of behavior.

Exploring the Experience of Teachers Working with Exceptional Learners

Regular classroom teachers, who often report that they lack adequate training and resources, increasingly find themselves supporting students with special education needs (Connelly & Graham, 2009). Teachers working in challenging environments can thrive in their role and continue to experience professional growth and passion about their work with students with exceptionalities (Perry, Brenner, Collie, & Hofer, 2015). Thriving is one framework of psychological wellness that can provide insight into the experiences of teachers working with exceptional learners (Spreitzer & Porath, 2014). Chronic stress from occupational demands such as heavy workload and insufficient resources can negatively affect the wellbeing of teachers and lead to poor mental health (Desrumaux et al., 2015). Burnout and compassion fatigue are two constructs of poor mental health that can inform our understanding of teachers’ social and emotional experiences. The purpose of this study was to explore the social and emotional experiences of teachers working with exceptional learners in regular classrooms. The objective of this study was to describe the elements within teachers’ professional roles that they report contribute to their social and emotional experiences understood through the lenses of thriving, burnout, and compassion fatigue. Interviews were conducted with five teachers: one full-time in-service teacher and four teachers who are pursuing graduate studies in education. The theme of thriving emerged as a significant component of the interview with all five participants. All five participants described experiences of vitality and learning as essential to their workplace satisfaction and overall thriving. Although the data from this study did not suggest that participants were experiencing burnout or compassion fatigue, elements of the two constructs did emerge as relevant to the social-emotional experiences of the teachers.

PROLINE-BASED CHIRAL STATIONARY PHASES: INSIGHTS INTO THE MECHANISM OF CHIRAL SELECTIVITY

Proline (Pro) is a unique amino acid that has been examined previously as a potential chiral selector for high-performance liquid chromatography. In recent years, a new class of promising Pro based enantioselective stationary phases has been studied and the longer peptides were found to be competitive with commercial chiral stationary phases (CSPs). Here, we aim to perform a comprehensive examination of a t-butoxycarbonyl- (t-Boc-) terminated monoproline selector. This selector was grafted through an amide linkage to an aminopropyl siloxane-terminated Si (111) wafer and to a silicon atomic force microscopy tip. To ensure a flat, homogeneous overlayer of selectors suitable for force spectrometric measurements, the prepared surfaces were characterized using XPS, AFM and contact angle measurements. Chemical force spectrometry (CFS) has been used to examine the chiral discrimination in our monoproline CSP by measuring the interaction forces between two D- or L-monoproline monolayers in water and in the presence of a series of amino acids in solution to explore the degree to which binding of amino acids impacts self-selectivity. Chemical force titration (CFT) has been used to observe the influence of variations in pH on the binding interaction of proline modified chiral surfaces. Here we aim to explore the connection between side-chain hydrophobicity and differences in the nature of the binding between different ionic forms of amino acids and the t-Boc-Pro interface, and thereby to gain insight into the mechanism of chiral selectivity. The CFS results show several trends for different proline selector/amino acid combinations and indicate that the binding characteristics of amino acid to the proline surface is strongly dependent on the amino acid side chain where hydrophilic side chain amino acids exhibit a selectivity opposite to that seen for those with hydrophobic side chains. The CFT studies also provide valuable insights into interactions between the proline selector and the amino acids under a wide range of pH conditions, indicating that protonated amine groups of alanine and serine are closely involved in the binding mechanism to proline surfaces. On the other hand, the presence of the second carboxylic group in aspartic acid plays an important role while interacting with proline.

INVESTIGATIVE COMPARISON OF TANK AND RECOVERED ASPHALT SAMPLES THROUGH PHYSICAL PERFORMANCE TESTING AND CHEMICAL ANALYSIS

Despite the development of improved performance test protocols by renowned researchers, there are still road networks which experience premature cracking and failure. One area of major concern in asphalt science and technology, especially in cold regions in Canada is thermal (low temperature) cracking. Usually right after winter periods, severe cracks are seen on poorly designed road networks. Quality assurance tests based on improved asphalt performance protocols have been implemented by government agencies to ensure that roads being constructed are at the required standard but asphalt binders that pass these quality assurance tests still crack prematurely. While it would be easy to question the competence of the quality assurance test protocols, it should be noted that performance tests which are being used and were repeated in this study, namely the extended bending beam rheometer (EBBR) test, double edge-notched tension test (DENT), dynamic shear rheometer (DSR) test and X-ray fluorescence (XRF) analysis have all been verified and proven to successfully predict asphalt pavement behaviour in the field. Hence this study looked to probe and test the quality and authenticity of the asphalt binders being used for road paving. This study covered thermal cracking and physical hardening phenomenon by comparing results from testing asphalt binder samples obtained from the storage ‘tank’ prior to paving (tank samples) and recovered samples for the same contracts with aim of explaining why asphalt binders that have passed quality assurance tests are still prone to fail prematurely. The study also attempted to find out if the short testing time and automated procedure of torsion bar experiments can replace the established but tedious procedure of the EBBR. In the end, it was discovered that significant differences in performance and composition exist between tank and recovered samples for the same contracts. Torsion bar experimental data also indicated some promise in predicting physical hardening.

CLASHES IN CONFINEMENT: MEN’S GENDERED EXPERIENCES WITH CONFLICT IN CANADIAN PRISONS

This dissertation presents the results of in-depth qualitative interviews with twenty-three formerly imprisoned men regarding their lived experience with prison conflict and the pain of incarceration. The results suggest that prison is a gendered ‘total institution’ (Goffman 1961). The pains that men experience in prison are uniquely gendered in that the deprivations imposed by incarceration– deprivation of autonomy, liberty, goods and services, heterosexual sex, and security (Sykes 1958) – in the reverse, define idealized masculinity as it is currently socially constructed: self-reliance, independence, toughness or invulnerability, material and economic success, and heterosexual prowess. From these shared deprivations emerges a gendered code of conduct that perpetuates a hierarchy among incarcerated men by constructing violent masculinity as a subcultural norm. The results suggest that the gender code in prison represents a set of rules that create opportunities for men to police each other’s gender performance and make claims to masculine statuses. Because status is inextricably tied to survival in this context, many men feel pressured to perform violent masculinities in prison despite privately subscribing to a non-violent sense of self-concept. The results suggest that violence is an expressive and instrumental resource for men in prison. A gender theory of prison violence, methodological findings, theoretical implications, ethical considerations and the short and long term aftermath of violent prison conflict are discussed.

Classifying And Predicting Software Security Vulnerabilities based on Reproducibility

Security defects are common in large software systems because of their size and complexity. Although efficient development processes, testing, and maintenance policies are applied to software systems, there are still a large number of vulnerabilities that can remain, despite these measures. Some vulnerabilities stay in a system from one release to the next one because they cannot be easily reproduced through testing. These vulnerabilities endanger the security of the systems. We propose vulnerability classification and prediction frameworks based on vulnerability reproducibility. The frameworks are effective to identify the types and locations of vulnerabilities in the earlier stage, and improve the security of software in the next versions (referred to as releases). We expand an existing concept of software bug classification to vulnerability classification (easily reproducible and hard to reproduce) to develop a classification framework for differentiating between these vulnerabilities based on code fixes and textual reports. We then investigate the potential correlations between the vulnerability categories and the classical software metrics and some other runtime environmental factors of reproducibility to develop a vulnerability prediction framework. The classification and prediction frameworks help developers adopt corresponding mitigation or elimination actions and develop appropriate test cases. Also, the vulnerability prediction framework is of great help for security experts focus their effort on the top-ranked vulnerability-prone files. As a result, the frameworks decrease the number of attacks that exploit security vulnerabilities in the next versions of the software. To build the classification and prediction frameworks, different machine learning techniques (C4.5 Decision Tree, Random Forest, Logistic Regression, and Naive Bayes) are employed. The effectiveness of the proposed frameworks is assessed based on collected software security defects of Mozilla Firefox.