Effects of Exogenous Lipopolysaccharide Exposure on Bone Outcomes in Rodent Models

Chronic low-grade inflammation has been identified as a potential contributor to the pathophysiology of osteoporosis. A key mediator may be lipopolysaccharide (LPS) released from gram-negative bacteria in the gut that can enter circulation stimulating an inflammatory response and upregulate bone resorption. Since rodent models mimic the loss of bone mineral density (BMD) and structure that occurs in humans, rodents offer an accelerated model for studying these inflammation-mediated changes. Therefore, the objective of this thesis was to characterize a rodent model of LPS-induced bone loss using repeated in vivo μCT scans to establish a time course effect of LPS longitudinally and for this purpose three studies were conducted. Study 1 & 2 were run simultaneously using the same control mice. Study 1 demonstrated that repeated irradiation had a negative impact on trabecular bone in both male and female CD-1 mice, while cortical bone was only negatively impacted in the females. In study 2, continuous delivery of exogenous LPS via osmotic pumps for 12 weeks elevated serum LPS in both male and female CD-1 mice but did not alter trabecular or cortical bone structure or BMD at any of the scanning timepoints. Results from Study 2 may in part have been influenced by the effects of repeated irradiation from the in vivo μCT scans at 4-week intervals for a total of 4 scans analyzed in Study 1. In study 3, a systematic review was conducted to better characterize a model of LPS induced bone loss and identify factors that may impact the effects of LPS on bone outcomes in rodent models. Regardless of study duration, exogenous LPS negatively impacted trabecular bone structure and BMD but not cortical bone structure, due to an upregulation in bone resorption. Together these data suggest that exogenous LPS can induce alterations in bone structure and BMD in rodent models, however a clearly defined model of exogenous LPS induced bone loss has yet to be fully characterized

Design of a distributed memory unit for clustered microarchitectures

Power constraints led to the end of exponential growth in single–processor performance, which characterized the semiconductor industry for many years. Single–chip multiprocessors allowed the performance growth to continue so far. Yet, Amdahl’s law asserts that the overall performance of future single–chip multiprocessors will depend crucially on single–processor performance. In a multiprocessor a small growth in single–processor performance can justify the use of significant resources. Partitioning the layout of critical components can improve the energy–efficiency and ultimately the performance of a single processor. In a clustered microarchitecture parts of these components form clusters. Instructions are processed locally in the clusters and benefit from the smaller size and complexity of the clusters components. Because the clusters together process a single instruction stream communications between clusters are necessary and introduce an additional cost. This thesis proposes the design of a distributed memory unit and first level cache in the context of a clustered microarchitecture. While the partitioning of other parts of the microarchitecture has been well studied the distribution of the memory unit and the cache has received comparatively little attention. The first proposal consists of a set of cache bank predictors. Eight different predictor designs are compared based on cost and accuracy. The second proposal is the distributed memory unit. The load and store queues are split into smaller queues for distributed disambiguation. The mapping of memory instructions to cache banks is delayed until addresses have been calculated. We show how disambiguation can be implemented efficiently with unordered queues. A bank predictor is used to map instructions that consume memory data near the data origin. We show that this organization significantly reduces both energy usage and latency. The third proposal introduces Dispatch Throttling and Pre-Access Queues. These mechanisms avoid load/store queue overflows that are a result of the late allocation of entries. The fourth proposal introduces Memory Issue Queues, which add functionality to select instructions for execution and re-execution to the memory unit. The fifth proposal introduces Conservative Deadlock Aware Entry Allocation. This mechanism is a deadlock safe issue policy for the Memory Issue Queues. Deadlocks can result from certain queue allocations because entries are allocated out-of-order instead of in-order like in traditional architectures. The sixth proposal is the Early Release of Load Queue Entries. Architectures with weak memory ordering such as Alpha, PowerPC or ARMv7 can take advantage of this mechanism to release load queue entries before the commit stage. Together, these proposals allow significantly smaller and more energy efficient load queues without the need of energy hungry recovery mechanisms and without performance penalties. Finally, we present a detailed study that compares the proposed distributed memory unit to a centralized memory unit and confirms its advantages of reduced energy usage and of improved performance

Power Consumption Analysis, Measurement, Management, and Issues:A State-of-the-Art Review of Smartphone Battery and Energy Usage

The advancement and popularity of smartphones have made it an essential and all-purpose device. But lack of advancement in battery technology has held back its optimum potential. Therefore, considering its scarcity, optimal use and efficient management of energy are crucial in a smartphone. For that, a fair understanding of a smartphone's energy consumption factors is necessary for both users and device manufacturers, along with other stakeholders in the smartphone ecosystem. It is important to assess how much of the device's energy is consumed by which components and under what circumstances. This paper provides a generalized, but detailed analysis of the power consumption causes (internal and external) of a smartphone and also offers suggestive measures to minimize the consumption for each factor. The main contribution of this paper is four comprehensive literature reviews on: 1) smartphone's power consumption assessment and estimation (including power consumption analysis and modelling); 2) power consumption management for smartphones (including energy-saving methods and techniques); 3) state-of-the-art of the research and commercial developments of smartphone batteries (including alternative power sources); and 4) mitigating the hazardous issues of smartphones' batteries (with a details explanation of the issues). The research works are further subcategorized based on different research and solution approaches. A good number of recent empirical research works are considered for this comprehensive review, and each of them is succinctly analysed and discussed

Integration and automation of a micro-tissue and microsphere based tissue engineering system and its application in cartilage regeneration and cancer models

Bottom-up biofabrication approaches for fabricating engineered tissue constructs are emerging strategies in tissue engineering. Few technologies have been developed that are capable of assembling tissue units into 3D Plotted scaffolds. We developed an integrated and automated 3D Bioassembly system for bioassembling engineered tissue constructs. The developed automated bioassembly system consisted of a (i) singularisation module and (ii) an injection module integrated into a commercial 3D bioprinter. The fluidic-based singularisation module delivered single Ø1 mm sized tissue unit at a time to the injection module and the injection module together with the 3D positioning system of the 3D bioprinter delivered the tissue unit into a predefined pore in the 3D Plotted scaffold. The developed automated bioassembly system was capable of either fabricating a construct via a two-step top-down bioassembly approach (fabricating a complete scaffold and insertion of tissue units) or a multistep bottom-up bioassembly approach (alternative layer-by-layer scaffold fabrication and tissue unit co-assembly). The automated bioassembly system was validated for application in cartilage and tumour engineering using tissue units (microspheres and micro-tissues). For cartilage engineering, Ø1 mm sized cartilage micro-tissues were fabricated utilising a previously demonstrated high-throughput 96-well plate format and Ø1 mm sized chondrocytes or chondroprogenitor cells-laden GelMA (gelatin-methacryloyl)-HepMA (methacrylated heparin) (9.5%-0.5%) hydrogel microspheres were fabricated utilising an adopted microfluidic system. For tumour engineering, a co-culture of cancer cells with fibroblasts using a liquid overlay technique was required to fabricate compact spherical Ø1 mm micro-tissues that could be handled by the automated bioassembly system and cancer cell-laden 10% GelMA hydrogel microspheres were fabricated utilising the adopted microfluidic system. Reliable handling of the tissue units was demonstrated by the automated bioassembly system. Bottom-up bioassembly of tissue units into 3D Plotted PEGT/PBT polymer scaffolds was demonstrated with the automated bioassembly system. No difference in viability was observed between the constructs assembled manually and with the automated bioassembly system. The flexibility of the automated tissue bioassembly system was shown by assembling constructs with coloured microspheres (denoting microspheres of different types) in various desired arrangements. The automated bioassembly of an anatomically shaped construct was also demonstrated. Neocartilage formation was observed in the chondrocyte-laden individual microspheres and assembled constructs when cultured in vitro for 35 days. Neocartilage formation was also visualised in the assembled graduated constructs fabricated with human articular chondrocytes (HAC) and mesenchymal stromal cells (MSC). In the in vitro micro-tissue tumour model, individual micro-tissues had higher chemoresistance compared to cells in 2D and the co-culture assembled construct had higher chemoresistance compared to individual co-culture micro-tissues. Similarly, in the in vitro microsphere tumour model, the assembled constructs were the most chemoresistant followed by individual microspheres and the cell in 2D had the lowest chemoresistance. The novel and flexible automated bioassembly technology that we have developed provides a pathway for fabricating a larger number of anatomically shaped clinically relevant constructs with precise control of the spatial position of the tissues units for application in cartilage engineering and for fabricating in vitro cancer models for application for drug discovery and high-throughput screening

Smart Sensors for Healthcare and Medical Applications

This book focuses on new sensing technologies, measurement techniques, and their applications in medicine and healthcare. Specifically, the book briefly describes the potential of smart sensors in the aforementioned applications, collecting 24 articles selected and published in the Special Issue “Smart Sensors for Healthcare and Medical Applications”. We proposed this topic, being aware of the pivotal role that smart sensors can play in the improvement of healthcare services in both acute and chronic conditions as well as in prevention for a healthy life and active aging. The articles selected in this book cover a variety of topics related to the design, validation, and application of smart sensors to healthcare

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018