Protein structure-based design of potent orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease.

A class of potent nonpeptidic inhibitors of human immunodeficiency virus protease has been designed by using the three-dimensional structure of the enzyme as a guide. By employing iterative protein cocrystal structure analysis, design, and synthesis the binding affinity of the lead compound was incrementally improved by over four orders of magnitude. An inversion in inhibitor binding mode was observed crystallographically, providing information critical for subsequent design and highlighting the utility of structural feedback in inhibitor optimization. These inhibitors are selective for the viral protease enzyme, possess good antiviral activity, and are orally available in three species.

3D teaching: the ideal complement for professionals in design and construction

Today, the requirement of professional skills to university students is constantly increasing in our society. In our opinion, the content offered in official degrees need to be nourished with different variables, enriching their global professional knowledge in a parallel way; that is why, in recent years, there is a great multiplicity of complementary courses at university. One of the most socially demanded technical requirements within the architectural, design or engineering field is the management of 3D drawing software, becoming an indispensable reality in these sectors. Thus, this specific training becomes essential over two-dimension traditional design, because the inclusion of great possibilities of spatial development that go beyond conventional orthographic projections (plans, sections or elevations), allowing modelling and rotation of the selected items from multiple angles and perspectives. Therefore, this paper analyzes the teaching methodology of a complementary course for those technicians in the construction industry interested in computer-aided design, using modelling (SketchupMake) and rendering programs (Kerkythea). The course is developed from the technician point of view, by learning computer management and its application to professional development from a more general to a more specific view through practical examples. The proposed methodology is based on the development of real examples in different professional environments such as rehabilitation, new constructions, opening projects or architectural design. This multidisciplinary contribution improves criticism of students in different areas, encouraging new learning strategies and the independent development of three-dimensional solutions. Thus, the practical implementation of new situations, even suggested by the students themselves, ensures active participation, saving time during the design process and the increase of effectiveness when generating elements which may be represented, moved or virtually tested. In conclusion, this teaching-learning methodology improves the skills and competencies of students to face the growing professional demands of society. After finishing the course, technicians not only improved their expertise in the field of drawing but they also enhanced their capacity for spatial vision; both essential qualities in these sectors that can be applied to their professional development with great success.

Aplicación del dibujo arquitectónico en 3D para el análisis histórico de los sistemas constructivos industrializados

La condición tridimensional de la construcción edificatoria precisa del uso del dibujo en 3D como la mejor herramienta de proyecto y transmisión de conocimientos técnicos y formales. El objetivo de esta comunicación es mostrar la aplicación de la expresión gráfica en 3D en un análisis histórico sobre la evolución de la envolvente industrializada en arquitectura, identificando sus principales condicionantes técnicos y constructivos. El estudio compara la evolución del uso de sistemas constructivos industrializados mediante un análisis gráfico de las soluciones constructivas más destacables. La metodología empleada se basa en la identificación y estudio de determinados sistemas constructivos industrializados compuestos por materiales ligeros así como de obras de arquitectura representativas por su influencia en la evolución de la envolvente arquitectónica en la segunda mitad del siglo XX. La representación gráfica en 3D ayuda a comparar las obras analizadas desde aspectos tecnológicos y formales, constatándose la utilidad del dibujo asistido por ordenador en el análisis constructivo realizado. En conclusión, el uso del dibujo arquitectónico en 3D contribuye, por la mejor comprensión de las características espaciales de las soluciones constructivas, al análisis de las propiedades materiales y funcionales de los sistemas constructivos industrializados y su aplicación al diseño arquitectónico, ayudando a perfeccionar su conocimiento e incrementando la calidad constructiva y compromiso social de las propuestas arquitectónicas.

Determination of lifter design, speed and filling effects in AG mills by 3D DEM

The power required to operate large gyratory mills often exceeds 10 MW. Hence, optimisation of the power consumption will have a significant impact on the overall economic performance and environmental impact of the mineral processing plant. In most of the published models of tumbling mills (e.g. [Morrell, S., 1996. Power draw of wet tumbling mills and its relationship to charge dynamics, Part 2: An empirical approach to modelling of mill power draw. Trans. Inst. Mining Metall. (Section C: Mineral Processing Ext. Metall.) 105, C54-C62. Austin, L.G., 1990. A mill power equation for SAG mills. Miner. Metall. Process. 57-62]), the effect of lifter design and its interaction with mill speed and filling are not incorporated. Recent experience suggests that there is an opportunity for improving grinding efficiency by choosing the appropriate combination of these variables. However, it is difficult to experimentally determine the interactions of these variables in a full scale mill. Although some work has recently been published using DEM simulations, it was basically. limited to 2D. The discrete element code, Particle Flow Code 3D (PFC3D), has been used in this work to model the effects of lifter height (525 cm) and mill speed (50-90% of critical) on the power draw and frequency distribution of specific energy (J/kg) of normal impacts in a 5 m diameter autogenous (AG) mill. It was found that the distribution of the impact energy is affected by the number of lifters, lifter height, mill speed and mill filling. Interactions of lifter design, mill speed and mill filling are demonstrated through three dimensional distinct element methods (3D DEM) modelling. The intensity of the induced stresses (shear and normal) on lifters, and hence the lifter wear, is also simulated. (C) 2004 Elsevier Ltd. All rights reserved.

A novel phantom and method for comprehensive 3-dimensional measurement and correction of geometric distortion in magnetic resonance imaging

A phantom that can be used for mapping geometric distortion in magnetic resonance imaging (MRI) is described. This phantom provides an array of densely distributed control points in three-dimensional (3D) space. These points form the basis of a comprehensive measurement method to correct for geometric distortion in MR images arising principally from gradient field non-linearity and magnet field inhomogeneity. The phantom was designed based on the concept that a point in space can be defined using three orthogonal planes. This novel design approach allows for as many control points as desired. Employing this novel design, a highly accurate method has been developed that enables the positions of the control points to be measured to sub-voxel accuracy. The phantom described in this paper was constructed to fit into a body coil of a MRI scanner, (external dimensions of the phantom were: 310 mm x 310 mm x 310 mm), and it contained 10,830 control points. With this phantom, the mean errors in the measured coordinates of the control points were on the order of 0.1 mm or less, which were less than one tenth of the voxel's dimensions of the phantom image. The calculated three-dimensional distortion map, i.e., the differences between the image positions and true positions of the control points, can then be used to compensate for geometric distortion for a full image restoration. It is anticipated that this novel method will have an impact on the applicability of MRI in both clinical and research settings. especially in areas where geometric accuracy is highly required, such as in MR neuro-imaging. (C) 2004 Elsevier Inc. All rights reserved.

Design of artificial myocardial microtissues

Cultivation technologies promoting organization of mammalian cells in three dimensions are essential for gene-function analyses as well as drug testing and represent the first step toward the design of tissue replacements and bioartificial organs. Embedded in a three-dimensional environment, cells are expected to develop tissue-like higher order intercellular structures (cell-cell contacts, extracellular matrix) that orchestrate cellular functions including proliferation, differentiation, apoptosis, and angiogenesis with unmatched quality. We have refined the hanging drop cultivation technology to pioneer beating heart microtissues derived from pure primary rat and mouse cardiomyocyte cultures as well as mixed populations reflecting the cell type composition of rodent hearts. Phenotypic characterization combined with detailed analysis of muscle-specific cell traits, extracellular matrix components, as well as endogenous vascular endothelial growth factor (VEGF) expression profiles of heart microtissues revealed (1) a linear cell number-microtissue size correlation, (2) intermicrotissue superstructures, (3) retention of key cardiomyocyte-specific cell qualities, (4) a sophisticated extracellular matrix, and (5) a high degree of self-organization exemplified by the tendency of muscle structures to assemble at the periphery of these myocardial spheroids. Furthermore (6), myocardial spheroids support endogenous VEGF expression in a size-dependent manner that will likely promote vascularization of heart microtissues produced from defined cell mixtures as well as support connection to the host vascular system after implantation. As cardiomyocytes are known to be refractory to current transfection technologies we have designed lentivirus-based transduction strategies to lead the way for genetic engineering of myocardial microtissues in a clinical setting.

Studies in three phase gas-liquid-solid fluidised systems

The work is a logical continuation of research started at Aston some years ago when studies were conducted on fermentations in bubble columns. The present work highlights typical design and operating problems that could arise in such systems as waste water, chemical, biochemical and petroleum operations involving three-phase, gas-liquid-solid fluidisation; such systems are in increasing use. It is believed that this is one of few studies concerned with `true' three-phase, gas-liquid-solid fluidised systems, and that this work will contribute significantly to closing some of the gaps in knowledge in this area. The research work was mainly experimentally based and involved studies of the hydrodynamic parameters, phase holdups (gas and solid), particle mixing and segregation, and phase flow dynamics (flow regime and circulation patterns). The studies have focused particularly on the solid behaviour and the influence of properties of solids present on the above parameters in three-phase, gas-liquid-solid fluidised systems containing single particle components and those containing binary and ternary mixtures of particles. All particles were near spherical in shape and two particle sizes and total concentration levels were used. Experiments were carried out in two- and three-dimensional bubble columns. Quantitative results are presented in graphical form and are supported by qualitative results from visual studies which are also shown as schematic diagrams and in photographic form. Gas and solid holdup results are compared for air-water containing single, binary and ternary component particle mixtures. It should be noted that the criteria for selection of the materials used are very important if true three-phase fluidisation is to be achieved: this is very evident when comparing the results with those in the literature. The fluid flow and circulation patterns observed were assessed for validation of the generally accepted patterns, and the author believes that the present work provides more accurate insight into the modelling of liquid circulation in bubble columns. The characteristic bubbly flow at low gas velocity in a two-phase system is suppressed in the three-phase system. The degree of mixing within the system is found to be dependent on flow regime, liquid circulation and the ratio of solid phase physical properties. Evidence of strong `trade-off' of properties is shown; the overall solid holdup is believed to be a major parameter influencing the gas holdup structure.

Design, fabrication, and evaluation of on-chip micro-supercapacitors

Due to the increasing demand for high power and reliable miniaturized energy storage devices, the development of micro-supercapacitors or electrochemical micro-capacitors have attracted much attention in recent years. This dissertation investigates several strategies to develop on-chip micro-supercapacitors with high power and energy density. Micro-supercapacitors based on interdigitated carbon micro-electrode arrays are fabricated through carbon microelectromechanical systems (C-MEMS) technique which is based on carbonization of patterned photoresist. To improve the capacitive behavior, electrochemical activation is performed on carbon micro-electrode arrays. The developed micro-supercapacitors show specific capacitances as high as 75 mFcm-2 at a scan rate of 5 mVs -1 after electrochemical activation for 30 minutes. The capacitance loss is less than 13% after 1000 cyclic voltammetry (CV) cycles. These results indicate that electrochemically activated C-MEMS micro-electrode arrays are promising candidates for on-chip electrochemical micro-capacitor applications. The energy density of micro-supercapacitors was further improved by conformal coating of polypyrrole (PPy) on C-MEMS structures. In these types of micro-devices the three dimensional (3D) carbon microstructures serve as current collectors for high energy density PPy electrodes. The electrochemical characterizations of these micro-supercapacitors show that they can deliver a specific capacitance of about 162.07 mFcm-2 and a specific power of 1.62mWcm -2 at a 20 mVs-1 scan rate. Addressing the need for high power micro-supercapacitors, the application of graphene as electrode materials for micro-supercapacitor was also investigated. The present study suggests a novel method to fabricate graphene-based micro-supercapacitors with thin film or in-plane interdigital electrodes. The fabricated micro-supercapacitors show exceptional frequency response and power handling performance and could effectively charge and discharge at rates as high as 50 Vs-1. CV measurements show that the specific capacitance of the micro-supercapacitor based on reduced graphene oxide and carbon nanotube composites is 6.1 mFcm -2 at scan rate of 0.01Vs-1. At a very high scan rate of 50 Vs-1, a specific capacitance of 2.8 mFcm-2 (stack capacitance of 3.1 Fcm-3) is recorded. This unprecedented performance can potentially broaden the future applications of micro-supercapacitors.

Physical Insights, Steady Aerodynamic Effects, and a Design Tool for Low-Pressure Turbine Flutter

The successful, efficient, and safe turbine design requires a thorough understanding of the underlying physical phenomena. This research investigates the physical understanding and parameters highly correlated to flutter, an aeroelastic instability prevalent among low pressure turbine (LPT) blades in both aircraft engines and power turbines. The modern way of determining whether a certain cascade of LPT blades is susceptible to flutter is through time-expensive computational fluid dynamics (CFD) codes. These codes converge to solution satisfying the Eulerian conservation equations subject to the boundary conditions of a nodal domain consisting fluid and solid wall particles. Most detailed CFD codes are accompanied by cryptic turbulence models, meticulous grid constructions, and elegant boundary condition enforcements all with one goal in mind: determine the sign (and therefore stability) of the aerodynamic damping. The main question being asked by the aeroelastician, ``is it positive or negative?'' This type of thought-process eventually gives rise to a black-box effect, leaving physical understanding behind. Therefore, the first part of this research aims to understand and reveal the physics behind LPT flutter in addition to several related topics including acoustic resonance effects. A percentage of this initial numerical investigation is completed using an influence coefficient approach to study the variation the work-per-cycle contributions of neighboring cascade blades to a reference airfoil. The second part of this research introduces new discoveries regarding the relationship between steady aerodynamic loading and negative aerodynamic damping. Using validated CFD codes as computational wind tunnels, a multitude of low-pressure turbine flutter parameters, such as reduced frequency, mode shape, and interblade phase angle, will be scrutinized across various airfoil geometries and steady operating conditions to reach new design guidelines regarding the influence of steady aerodynamic loading and LPT flutter. Many pressing topics influencing LPT flutter including shocks, their nonlinearity, and three-dimensionality are also addressed along the way. The work is concluded by introducing a useful preliminary design tool that can estimate within seconds the entire aerodynamic damping versus nodal diameter curve for a given three-dimensional cascade.

Design of Latent Thermal Energy Storage Systems

This dissertation documents the results of a theoretical and numerical study of time dependent storage of energy by melting a phase change material. The heating is provided along invading lines, which change from single-line invasion to tree-shaped invasion. Chapter 2 identifies the special design feature of distributing energy storage in time-dependent fashion on a territory, when the energy flows by fluid flow from a concentrated source to points (users) distributed equidistantly on the area. The challenge in this chapter is to determine the architecture of distributed energy storage. The chief conclusion is that the finite amount of storage material should be distributed proportionally with the distribution of the flow rate of heating agent arriving on the area. The total time needed by the source stream to ‘invade’ the area is cumulative (the sum of the storage times required at each storage site), and depends on the energy distribution paths and the sequence in which the users are served by the source stream. Chapter 3 shows theoretically that the melting process consists of two phases: “invasion” thermal diffusion along the invading line, which is followed by “consolidation” as heat diffuses perpendicularly to the invading line. This chapter also reports the duration of both phases and the evolution of the melt layer around the invading line during the two-dimensional and three-dimensional invasion. It also shows that the amount of melted material increases in time according to a curve shaped as an S. These theoretical predictions are validated by means of numerical simulations in chapter 4. This chapter also shows that the heat transfer rate density increases (i.e., the S curve becomes steeper) as the complexity and number of degrees of freedom of the structure are increased, in accord with the constructal law. The optimal geometric features of the tree structure are detailed in this chapter. Chapter 5 documents a numerical study of time-dependent melting where the heat transfer is convection dominated, unlike in chapter 3 and 4 where the melting is ruled by pure conduction. In accord with constructal design, the search is for effective heat-flow architectures. The volume-constrained improvement of the designs for heat flow begins with assuming the simplest structure, where a single line serves as heat source. Next, the heat source is endowed with freedom to change its shape as it grows. The objective of the numerical simulations is to discover the geometric features that lead to the fastest melting process. The results show that the heat transfer rate density increases as the complexity and number of degrees of freedom of the structure are increased. Furthermore, the angles between heat invasion lines have a minor effect on the global performance compared to other degrees of freedom: number of branching levels, stem length, and branch lengths. The effect of natural convection in the melt zone is documented.

CAD Files and European Design Law

Three-dimensional printing (“3DP”) is an additive manufacturing technology that starts with a virtual 3D model of the object to be printed, the so-called Computer-Aided-Design (“CAD”) file. This file, when sent to the printer, gives instructions to the device on how to build the object layer-by-layer. This paper explores whether design protection is available under the current European regulatory framework for designs that are computer-created by means of CAD software, and, if so, under what circumstances. The key point is whether the appearance of a product, embedded in a CAD file, could be regarded as a protectable element under existing legislation. To this end, it begins with an inquiry into the concepts of “design” and “product”, set forth in Article 3 of the Community Design Regulation No. 6/2002 (“CDR”). Then, it considers the EUIPO’s practice of accepting 3D digital representations of designs. The enquiry goes on to illustrate the implications that the making of a CAD file available online might have. It suggests that the act of uploading a CAD file onto a 3D printing platform may be tantamount to a disclosure for the purposes of triggering unregistered design protection, and for appraising the state of the prior art. It also argues that, when measuring the individual character requirement, the notion of “informed user” and “the designer’s degree of freedom” may need to be reconsidered in the future. The following part touches on the exceptions to design protection, with a special focus on the repairs clause set forth in Article 110 CDR. The concluding part explores different measures that may be implemented to prohibit the unauthorised creation and sharing of CAD files embedding design-protected products.

Athletic groin pain (part 2): a prospective cohort study on the biomechanical evaluation of change of direction identifies three clusters of movement patterns

Background: Athletic groin pain (AGP) is prevalent in sports involving repeated accelerations, decelerations, kicking and change-of-direction movements. Clinical and radiological examinations lack the ability to assess pathomechanics of AGP, but three-dimensional biomechanical movement analysis may be an important innovation. Aim: The primary aim was to describe and analyse movements used by patients with AGP during a maximum effort change-of-direction task. The secondary aim was to determine if specific anatomical diagnoses were related to a distinct movement strategy. Methods: 322 athletes with a current symptom of chronic AGP participated. Structured and standardised clinical assessments and radiological examinations were performed on all participants. Additionally, each participant performed multiple repetitions of a planned maximum effort change-of-direction task during which whole body kinematics were recorded. Kinematic and kinetic data were examined using continuous waveform analysis techniques in combination with a subgroup design that used gap statistic and hierarchical clustering. Results: Three subgroups (clusters) were identified. Kinematic and kinetic measures of the clusters differed strongly in patterns observed in thorax, pelvis, hip, knee and ankle. Cluster 1 (40%) was characterised by increased ankle eversion, external rotation and knee internal rotation and greater knee work. Cluster 2 (15%) was characterised by increased hip flexion, pelvis contralateral drop, thorax tilt and increased hip work. Cluster 3 (45%) was characterised by high ankle dorsiflexion, thorax contralateral drop, ankle work and prolonged ground contact time. No correlation was observed between movement clusters and clinically palpated location of the participant's pain. Conclusions: We identified three distinct movement strategies among athletes with long-standing groin pain during a maximum effort change-of-direction task. These movement strategies were not related to clinical assessment findings but highlighted targets for rehabilitation in response to possible propagative mechanisms. Trial registration number NCT02437942, pre results.

Design of Streaming Media Panoramic Video System Based on WebGL

2016 is the outbreak year of the virtual reality industry. In the field of virtual reality, 3D surveying plays an important role. Nowadays, 3D surveying technology has received increasing attention. This project aims to establish and optimize a WebGL three-dimensional broadcast platform combined with streaming media technology. It takes streaming media server and panoramic video broadcast in browser as the application background. Simultaneously, it discusses about the architecture from streaming media server to panoramic media player and analyzing relevant theory problem. This paper focuses on the debugging of streaming media platform, the structure of WebGL player environment, different types of ball model analysis, and the 3D mapping technology. The main work contains the following points: Initially, relay on Easy Darwin open source streaming media server, built a streaming service platform. It can realize the transmission from RTSP stream to streaming media server, and forwards HLS slice video to clients; Then, wrote a WebGL panoramic video player based on Three.js lib with JQuery browser playback controls. Set up a HTML5 panoramic video player; Next, analyzed the latitude and longitude sphere model which from Three.js library according to WebGL rendering method. Pointed out the drawbacks of this model and the breakthrough point of improvement; After that, on the basis of Schneider transform principle, established the Schneider sphere projection model, and converted the output OBJ file to JS file for media player reading. Finally implemented real time panoramic video high precision playing without plugin; At last, I summarized the whole project. Put forward the direction of future optimization and extensible market.

A narrativa histórica de Alexandre Wollner sobre o design brasileiro em sua relação com arte, indústria e tecnologia

This work aims to investigate the historical narratives in which the graphic designer Alexandre Wollner assembled about the development of its own profession in Brazil, focusing the ways in which his discourse points relations among design (with greater emphasis in graphic design) and visual arts, the industrial development and notions about technology. Firstly, the theoretical setup searched for dialogues with design historians, with Mikhail Bakhtin, specially his concepts about “ideology” and “discourse’, and the theory of Field Autonomy by Pierre Bourdieu applied in the artistic practice. Following, the relation between Wollner’s own journey and the Brazilian industrial development is shown, and, at last, three of his historical texts are studied, which are written in different moments (1964; 1983; 1998), being those in which the analyzed author wished to point out the origens, events and names that are more remarkable. Throughout the work, it is pointed the importance of Wollner’s contact with the modernist european ideologies that share an abstract and rationalist matrix found at Hochschule für Gestaltung Ulm (HfG Ulm), the german design school from the city of Ulm, in the 1950s. Such modernist discourse understood the practice of design as a method with scientific character, being then different of some other more recurring artistic professional practices in some productive sectors. Wollner aimed to apply such ideals in his professional practice, being the foundation of the paulista office forminform, in 1958, one of his first expressions of such posture, and in his academic practice, helping the foundation of the Escola Superior de Desenho Industrial (ESDI), in Rio de Janeiro, in 1963. Such modernist ideals went along with moments of the Brazilian industrial development during the government of Juscelino Kubitschek (1956–1961) and the “Economical Miracle” from the military government (1968–1973). Wollner argued about the need for the development of national design as a technological and productive differential that would help the growth of national industry, based on Ulm’s project model concept. It is defended that Wollner’s professional and intelectual path, in his efforts of thinking a history of Brazilian design through the choice of pioneers in the area, was founded on an “ideal model” of design, leaving aside the modernist experiences from the 1950s. Such posture would indicate a search for validation of his own profession that was beginning to become more evident in Brazilian productive means, aiming the creation of a differential space in comparison with pre-established practices, usually link to graphic artists from the time.

Physical Design Methodologies for Low Power and Reliable 3D ICs

As the semiconductor industry struggles to maintain its momentum down the path following the Moore's Law, three dimensional integrated circuit (3D IC) technology has emerged as a promising solution to achieve higher integration density, better performance, and lower power consumption. However, despite its significant improvement in electrical performance, 3D IC presents several serious physical design challenges. In this dissertation, we investigate physical design methodologies for 3D ICs with primary focus on two areas: low power 3D clock tree design, and reliability degradation modeling and management. Clock trees are essential parts for digital system which dissipate a large amount of power due to high capacitive loads. The majority of existing 3D clock tree designs focus on minimizing the total wire length, which produces sub-optimal results for power optimization. In this dissertation, we formulate a 3D clock tree design flow which directly optimizes for clock power. Besides, we also investigate the design methodology for clock gating a 3D clock tree, which uses shutdown gates to selectively turn off unnecessary clock activities. Different from the common assumption in 2D ICs that shutdown gates are cheap thus can be applied at every clock node, shutdown gates in 3D ICs introduce additional control TSVs, which compete with clock TSVs for placement resources. We explore the design methodologies to produce the optimal allocation and placement for clock and control TSVs so that the clock power is minimized. We show that the proposed synthesis flow saves significant clock power while accounting for available TSV placement area. Vertical integration also brings new reliability challenges including TSV's electromigration (EM) and several other reliability loss mechanisms caused by TSV-induced stress. These reliability loss models involve complex inter-dependencies between electrical and thermal conditions, which have not been investigated in the past. In this dissertation we set up an electrical/thermal/reliability co-simulation framework to capture the transient of reliability loss in 3D ICs. We further derive and validate an analytical reliability objective function that can be integrated into the 3D placement design flow. The reliability aware placement scheme enables co-design and co-optimization of both the electrical and reliability property, thus improves both the circuit's performance and its lifetime. Our electrical/reliability co-design scheme avoids unnecessary design cycles or application of ad-hoc fixes that lead to sub-optimal performance. Vertical integration also enables stacking DRAM on top of CPU, providing high bandwidth and short latency. However, non-uniform voltage fluctuation and local thermal hotspot in CPU layers are coupled into DRAM layers, causing a non-uniform bit-cell leakage (thereby bit flip) distribution. We propose a performance-power-resilience simulation framework to capture DRAM soft error in 3D multi-core CPU systems. In addition, a dynamic resilience management (DRM) scheme is investigated, which adaptively tunes CPU's operating points to adjust DRAM's voltage noise and thermal condition during runtime. The DRM uses dynamic frequency scaling to achieve a resilience borrow-in strategy, which effectively enhances DRAM's resilience without sacrificing performance. The proposed physical design methodologies should act as important building blocks for 3D ICs and push 3D ICs toward mainstream acceptance in the near future.