ON THE INVESTIGATION OF MACHINE TOOL CHATTER IN THE MILLING PROCESS

ABSTRACT In this paper, the chatter phenomenon is investigated through a single degree of freedom model of the milling process. In this regard, the non-linear equation of motion obtained from modeling of the milling process, which is a time-periodic delay differential equation, is simulated, and by changing the parameters: spindle speed and depth of cut, and assuming constant quantities for other parameters of the system the stable and instable points for the system are gained according to these two parameters by numerical method. In the end, the stability chart for this system is plotted and the approximate boundaries between the stability and instability regions are obtained numerically

The role of mundane and subtle institutional work in market dynamics: a case of fashion clothing market

Research on market dynamics shows that markets (trans)form through the institutional work of a wide range of actors. This literature, however, focuses on resourceful and/or powerful actors who can freely and openly shape the market. Via an inductive analysis of the Iranian female fashion clothing market, we examine the institutional work undertaken by actors who have limited resources and are subject to power structures that constrain their institutional work. We find that consumers, designers, retailers, and social activists engage in ambidextrous practices, secure networks, and stealthy defiance to navigate or moderate their institutional restrictions. Such work contributes to the relaxation of some state regulations and the coexistence of parallel taste structures. The study draws attention to mundane, subtle, and less visible and organized institutional work and extends knowledge on marketplace resistance by showing that everyday acts of resistance can function as unintentional institutional work that contributes to market dynamics

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Development of Full-Length Ligand-Activated Split-Kinases and Split-Phosphatases for Interrogation of Signal Transduction Pathways

Reversible phosphorylation controls both temporal and spatial activity of proteins within almost all signaling cascades. The human complement of >500 protein kinases and 147 protein phosphatases regulate various cellular events from cell division to cell death. The aberrant function of these proteins is implicated in diseases such as cancer, metabolic disorder and neurodegeneration. Thus, understanding the function of a specific kinase or phosphatase, by turning them on or off, is important for understanding their biology and for designing new therapies. Toward this goal, a few emerging methods have made significant advances towards turning-on or turning-off the activity of a specific kinase. However, current methods do not necessarily allow for orthogonal control over two or more kinases or phosphatases in living cells. The major focus of this dissertation is the development of a new method for turning-on a specific kinase or phosphatase temporally, which can be used for orthogonal control of multiple kinases or phosphatases simultaneously. We hypothesized that if we could design fragmented split-kinases that can be turned on by different ligands then two or more kinases or phosphatases could be temporally controlled. We first developed a sequence dissimilarity-based approach to identify sites in the catalytic domain of kinases tolerant to a 25-residue loop insertion. The successful loop insertion sites, guided the fragmentation of the kinases at these sites into two inactive fragments, which were subsequently attached to two proteins, FKBP and FRB that dimerize in the presence of the small molecule, rapamycin. Previously we have demonstrated that the addition of rapamycin to the designed split-kinases could selectively turn-on enzymatic activity. Moreover we demonstrated that the split-enzyme approach could be extended to protein phosphatases. In this work we have successfully tested and extended the in vitro approach and designed several new split kinases and split-phosphatases. Initial studies were performed in an in vitro setting and focused on the catalytic domain of split-kinases and split-phosphatases. Importantly, we extend our design to full-length proteins and demonstrate that full-length split-kinases and split-phosphatases can be successfully controlled by addition of a small molecule ligand, rapamycin, in live cells. Moreover, the known downstream activity of full-length rapamycin-gated split-kinases, Src and Lyn, and the split-phosphatase, HePTP, were validated within signaling pathways. Thus, this work lays the foundation for future temporal interrogation of kinases and phosphatases implicated in a range of cellular pathways. Another section of the dissertation focuses on an interesting discovery that several of these split-kinases can be mixed and matched, where half of the new chimeric enzyme is derived from one parent kinase and the other half comes from a different parent kinase. This chimeric phenomenon has interesting implications for the evolution and design of protein kinases and the approach can potentially be used to design new chimeric-protein kinases. In summary, this work describes the design of ligand-activated split-kinases and split-phosphatases that can be used to study phosphorylation in living cells and potentially be used to rewire biological circuitry.Release after 12-Sep-201

Factors Influencing the Use of Autonomous and Shared Autonomous Vehicles in Alberta

Autonomous vehicles (AV) are expected to have a wide-ranging affect on traffic congestion, safety, comfort, car ownership, land use and the environment. In this thesis, stated preference survey was designed to examine people’s willingness to give up driving control to AVs and their willingness to use them as shared autonomous vehicles (SAV). The results indicate that Level 3 automation should be skipped and the market should move directly to full automation. People are willing to pay $3529,$2691 and $4349 per year for the fixed cost of AVs with Level 2, 3, and 4 automation. The early owners of AVs are males over 50 years old and the early adaptors of SAVs are males younger than 35 years old. Also, the willingness to use higher levels of automation is attributed to people’s perception towards AVs