DESIGN, MANUFACTURE, AND IMPLEMENTATION OF 3D-PRINTED TISSUE ENGINEERING SCAFFOLDS USED WITH STROMAL VASCULAR CELLS FOR CRANIOFACIAL BONE REGENERATION

Craniofacial bone defects have poor outcomes under current treatments: implants become infected, loosen, and displace; bone grafts resorb and weaken over time; and there are no satisfactory pediatric options. To improve outcomes, this thesis develops a novel osteoinductive biomaterial, the methods to 3D-print the biomaterial, and the tools to design of that 3D-printed scaffold for the mechanical loads of the craniofacial skeleton. Further, it combines the scaffold with key regenerative agents – autologous stem cells – to facilitate boney regeneration in the implanted scaffold. The feasibility of the scaffold and cells approach is tested by implementation in preclinical models and assessment of bone and vascular outcomes. Aim 1: To create an osteoinductive biomaterial, trabecular bone was decellularized, cryo-milled, and mixed with polycaprolactone. This thermoplastic material mixture was then 3D-printed and demonstrated osteoinductive effects on cells. Aim 2: As regenerative autologous cells, the stromal vascular fraction of adipose tissue was isolated in a point-of-care manner and timeframe and the stem cell yield, surface markers, in vitro and in vivo regenerative potential for vascular and bone tissue was demonstrated. Aim 3: Then the means to design 3D-print the biomaterial with controlled tissue engineering properties – pore size and porosity – at human craniofacial scales and for human physiologic loads was developed and tested. Aim 4: Finally, the biomaterial, cells, and design and manufacturing were implemented in a patient-specific, large-animal, preclinical model of zygomatic arch regeneration in swine. Implant design and manufacture was successfully validated, and the implanted scaffolds and cells showed a substantial bone regenerating response compared to untreated controls

Cost-Efficient Soft-Error Resiliency for ASIP-based Embedded Systems

Recent decades have witnessed the rapid growth of embedded systems. At present, embedded systems are widely applied in a broad range of critical applications including automotive electronics, telecommunication, healthcare, industrial electronics, consumer electronics military and aerospace. Human society will continue to be greatly transformed by the pervasive deployment of embedded systems. Consequently, substantial amount of efforts from both industry and academic communities have contributed to the research and development of embedded systems. Application-specific instruction-set processor (ASIP) is one of the key advances in embedded processor technology, and a crucial component in some embedded systems. Soft errors have been directly observed since the 1970s. As devices scale, the exponential increase in the integration of computing systems occurs, which leads to correspondingly decrease in the reliability of computing systems. Today, major research forums state that soft errors are one of the major design technology challenges at and beyond the 22 nm technology node. Therefore, a large number of soft-error solutions, including error detection and recovery, have been proposed from differing perspectives. Nonetheless, most of the existing solutions are designed for general or high-performance systems which are different to embedded systems. For embedded systems, the soft-error solutions must be cost-efficient, which requires the tailoring of the processor architecture with respect to the feature of the target application. This thesis embodies a series of explorations for cost-efficient soft-error solutions for ASIP-based embedded systems. In this exploration, five major solutions are proposed. The first proposed solution realizes checkpoint recovery in ASIPs. By generating customized instructions, ASIP-implemented checkpoint recovery can perform at a finer granularity than what was previously possible. The fault-free performance overhead of this solution is only 1.45% on average. The recovery delay is only 62 cycles at the worst case. The area and leakage power overheads are 44.4% and 45.6% on average. The second solution explores utilizing two primitive error recovery techniques jointly. This solution includes three application-specific optimization methodologies. This solution generates the optimized error-resilient ASIPs, based on the characteristics of primitive error recovery techniques, static reliability analysis and design constraints. The resultant ASIP can be configured to perform at runtime according to the optimized recovery scheme. This solution can strategically enhance cost-efficiency for error recovery. In order to guarantee cost-efficiency in unpredictable runtime situations, the third solution explores runtime adaptation for error recovery. This solution aims to budget and adapt the error recovery operations, so as to spend the resources intelligently and to tolerate adverse influences of runtime variations. The resultant ASIP can make runtime decisions to determine the activation of spatial and temporal redundancies, according to the runtime situations. At the best case, this solution can achieve almost 50x reliability gain over the state of the art solutions. Given the increasing demand for multi-core computing systems, the last two proposed solutions target error recovery in multi-core ASIPs. The first solution of these two explores ASIP-implemented fine-grained process migration. This solution is a key infrastructure, which allows cost-efficient task management, for realizing cost-efficient soft-error recovery in multi-core ASIPs. The average time cost is only 289 machine cycles to perform process migration. The last solution explores using dynamic and adaptive mapping to assign heterogeneous recovery operations to the tasks in the multi-core context. This solution allows each individual ASIP-based processing core to dynamically adapt its specific error recovery functionality according to the corresponding task's characteristics, in terms of soft error vulnerability and execution time deadline. This solution can significantly improve the reliability of the system by almost two times, with graceful constraint penalty, in comparison to the state-of-the-art counterparts

On the performance and programming of reversible molecular computers

If the 20th century was known for the computational revolution, what will the 21st be known for? Perhaps the recent strides in the nascent fields of molecular programming and biological computation will help bring about the ‘Coming Era of Nanotechnology’ promised in Drexler’s ‘Engines of Creation’. Though there is still far to go, there is much reason for optimism. This thesis examines the underlying principles needed to realise the computational aspects of such ‘engines’ in a performant way. Its main body focusses on the ways in which thermodynamics constrains the operation and design of such systems, and it ends with the proposal of a model of computation appropriate for exploiting these constraints. These thermodynamic constraints are approached from three different directions. The first considers the maximum possible aggregate performance of a system of computers of given volume, V, with a given supply of free energy. From this perspective, reversible computing is imperative in order to circumvent the Landauer limit. A result of Frank is refined and strengthened, showing that the adiabatic regime reversible computer performance is the best possible for any computer—quantum or classical. This therefore shows a universal scaling law governing the performance of compact computers of ~V^(5/6), compared to ~V^(2/3) for conventional computers. For the case of molecular computers, it is shown how to attain this bound. The second direction extends this performance analysis to the case where individual computational particles or sub-units can interact with one another. The third extends it to interactions with shared, non-computational parts of the system. It is found that accommodating these interactions in molecular computers imposes a performance penalty that undermines the earlier scaling result. Nonetheless, scaling superior to that of irreversible computers can be preserved, and appropriate mitigations and considerations are discussed. These analyses are framed in a context of molecular computation, but where possible more general computational systems are considered. The proposed model, the א-calculus, is appropriate for programming reversible molecular computers taking into account these constraints. A variety of examples and mathematical analyses accompany it. Moreover, abstract sketches of potential molecular implementations are provided. Developing these into viable schemes suitable for experimental validation will be a focus of future work

Functional Biodegradable Nanocomposites

Concern around environmental issues facing society has grown significantly in recent years. Reduction in damages resulting from both industrial and domestic waste has become a key topic as a means to address environmental problems and the exhaustion of natural resources. Likewise, the use of materials of polymeric origin in applications such as tissue regeneration, controlled release of medicines, packaging, soil remediation, etc., makes the development of materials biodegradable in biological media increasingly important. Recently, significant progress has been achieved in the creation of biodegradable polymeric formulations with functionalities similar to those of non-biodegradable polymers, both of natural and of synthetic origin, extending their applicability to fields such as food packaging, electronics, production of health-related materials, agriculture, etc. In this context, biodegradable nanocomposites offer new and exciting possibilities. This book deals with the development of functional polymer nanocomposites that can undergo biodegradation in different media, including biological systems, soils, landfills, etc. Original and review articles covering aspects of polymer science and technology, such as synthesis, processing, characterization, properties, and applications of functional biodegradable nanocomposites for different applications, are included in this book

Parallel and Distributed Computing

The 14 chapters presented in this book cover a wide variety of representative works ranging from hardware design to application development. Particularly, the topics that are addressed are programmable and reconfigurable devices and systems, dependability of GPUs (General Purpose Units), network topologies, cache coherence protocols, resource allocation, scheduling algorithms, peertopeer networks, largescale network simulation, and parallel routines and algorithms. In this way, the articles included in this book constitute an excellent reference for engineers and researchers who have particular interests in each of these topics in parallel and distributed computing

Adaptive Distributed Architectures for Future Semiconductor Technologies.

Year after year semiconductor manufacturing has been able to integrate more components in a single computer chip. These improvements have been possible through systematic shrinking in the size of its basic computational element, the transistor. This trend has allowed computers to progressively become faster, more efficient and less expensive. As this trend continues, experts foresee that current computer designs will face new challenges, in utilizing the minuscule devices made available by future semiconductor technologies. Today's microprocessor designs are not fit to overcome these challenges, since they are constrained by their inability to handle component failures by their lack of adaptability to a wide range of custom modules optimized for specific applications and by their limited design modularity. The focus of this thesis is to develop original computer architectures, that can not only survive these new challenges, but also leverage the vast number of transistors available to unlock better performance and efficiency. The work explores and evaluates new software and hardware techniques to enable the development of novel adaptive and modular computer designs. The thesis first explores an infrastructure to quantitatively assess the fallacies of current systems and their inadequacy to operate on unreliable silicon. In light of these findings, specific solutions are then proposed to strengthen digital system architectures, both through hardware and software techniques. The thesis culminates with the proposal of a radically new architecture design that can fully adapt dynamically to operate on the hardware resources available on chip, however limited or abundant those may be.PHDComputer Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/102405/1/apellegr_1.pd

Low-cost and efficient fault detection and diagnosis schemes for modern cores

Continuous improvements in transistor scaling together with microarchitectural advances have made possible the widespread adoption of high-performance processors across all market segments. However, the growing reliability threats induced by technology scaling and by the complexity of designs are challenging the production of cheap yet robust systems. Soft error trends are haunting, especially for combinational logic, and parity and ECC codes are therefore becoming insufficient as combinational logic turns into the dominant source of soft errors. Furthermore, experts are warning about the need to also address intermittent and permanent faults during processor runtime, as increasing temperatures and device variations will accelerate inherent aging phenomena. These challenges specially threaten the commodity segments, which impose requirements that existing fault tolerance mechanisms cannot offer. Current techniques based on redundant execution were devised in a time when high penalties were assumed for the sake of high reliability levels. Novel light-weight techniques are therefore needed to enable fault protection in the mass market segments. The complexity of designs is making post-silicon validation extremely expensive. Validation costs exceed design costs, and the number of discovered bugs is growing, both during validation and once products hit the market. Fault localization and diagnosis are the biggest bottlenecks, magnified by huge detection latencies, limited internal observability, and costly server farms to generate test outputs. This thesis explores two directions to address some of the critical challenges introduced by unreliable technologies and by the limitations of current validation approaches. We first explore mechanisms for comprehensively detecting multiple sources of failures in modern processors during their lifetime (including transient, intermittent, permanent and also design bugs). Our solutions embrace a paradigm where fault tolerance is built based on exploiting high-level microarchitectural invariants that are reusable across designs, rather than relying on re-execution or ad-hoc block-level protection. To do so, we decompose the basic functionalities of processors into high-level tasks and propose three novel runtime verification solutions that combined enable global error detection: a computation/register dataflow checker, a memory dataflow checker, and a control flow checker. The techniques use the concept of end-to-end signatures and allow designers to adjust the fault coverage to their needs, by trading-off area, power and performance. Our fault injection studies reveal that our methods provide high coverage levels while causing significantly lower performance, power and area costs than existing techniques. Then, this thesis extends the applicability of the proposed error detection schemes to the validation phases. We present a fault localization and diagnosis solution for the memory dataflow by combining our error detection mechanism, a new low-cost logging mechanism and a diagnosis program. Selected internal activity is continuously traced and kept in a memory-resident log whose capacity can be expanded to suite validation needs. The solution can catch undiscovered bugs, reducing the dependence on simulation farms that compute golden outputs. Upon error detection, the diagnosis algorithm analyzes the log to automatically locate the bug, and also to determine its root cause. Our evaluations show that very high localization coverage and diagnosis accuracy can be obtained at very low performance and area costs. The net result is a simplification of current debugging practices, which are extremely manual, time consuming and cumbersome. Altogether, the integrated solutions proposed in this thesis capacitate the industry to deliver more reliable and correct processors as technology evolves into more complex designs and more vulnerable transistors.El continuo escalado de los transistores junto con los avances microarquitectónicos han posibilitado la presencia de potentes procesadores en todos los segmentos de mercado. Sin embargo, varios problemas de fiabilidad están desafiando la producción de sistemas robustos. Las predicciones de "soft errors" son inquietantes, especialmente para la lógica combinacional: soluciones como ECC o paridad se están volviendo insuficientes a medida que dicha lógica se convierte en la fuente predominante de soft errors. Además, los expertos están alertando acerca de la necesidad de detectar otras fuentes de fallos (causantes de errores permanentes e intermitentes) durante el tiempo de vida de los procesadores. Los segmentos "commodity" son los más vulnerables, ya que imponen unos requisitos que las técnicas actuales de fiabilidad no ofrecen. Estas soluciones (generalmente basadas en re-ejecución) fueron ideadas en un tiempo en el que con tal de alcanzar altos nivel de fiabilidad se asumían grandes costes. Son por tanto necesarias nuevas técnicas que permitan la protección contra fallos en los segmentos más populares. La complejidad de los diseños está encareciendo la validación "post-silicon". Su coste excede el de diseño, y el número de errores descubiertos está aumentando durante la validación y ya en manos de los clientes. La localización y el diagnóstico de errores son los mayores problemas, empeorados por las altas latencias en la manifestación de errores, por la poca observabilidad interna y por el coste de generar las señales esperadas. Esta tesis explora dos direcciones para tratar algunos de los retos causados por la creciente vulnerabilidad hardware y por las limitaciones de los enfoques de validación. Primero exploramos mecanismos para detectar múltiples fuentes de fallos durante el tiempo de vida de los procesadores (errores transitorios, intermitentes, permanentes y de diseño). Nuestras soluciones son de un paradigma donde la fiabilidad se construye explotando invariantes microarquitectónicos genéricos, en lugar de basarse en re-ejecución o en protección ad-hoc. Para ello descomponemos las funcionalidades básicas de un procesador y proponemos tres soluciones de `runtime verification' que combinadas permiten una detección de errores a nivel global. Estas tres soluciones son: un verificador de flujo de datos de registro y de computación, un verificador de flujo de datos de memoria y un verificador de flujo de control. Nuestras técnicas usan el concepto de firmas y permiten a los diseñadores ajustar los niveles de protección a sus necesidades, mediante compensaciones en área, consumo energético y rendimiento. Nuestros estudios de inyección de errores revelan que los métodos propuestos obtienen altos niveles de protección, a la vez que causan menos costes que las soluciones existentes. A continuación, esta tesis explora la aplicabilidad de estos esquemas a las fases de validación. Proponemos una solución de localización y diagnóstico de errores para el flujo de datos de memoria que combina nuestro mecanismo de detección de errores, junto con un mecanismo de logging de bajo coste y un programa de diagnóstico. Cierta actividad interna es continuamente registrada en una zona de memoria cuya capacidad puede ser expandida para satisfacer las necesidades de validación. La solución permite descubrir bugs, reduciendo la necesidad de calcular los resultados esperados. Al detectar un error, el algoritmo de diagnóstico analiza el registro para automáticamente localizar el bug y determinar su causa. Nuestros estudios muestran un alto grado de localización y de precisión de diagnóstico a un coste muy bajo de rendimiento y área. El resultado es una simplificación de las prácticas actuales de depuración, que son enormemente manuales, incómodas y largas. En conjunto, las soluciones de esta tesis capacitan a la industria a producir procesadores más fiables, a medida que la tecnología evoluciona hacia diseños más complejos y más vulnerables