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With continued feature size reduction in microelectronics and with more than a billion transistors on a single integrated circuit (IC), on-chip interconnection has become a challenge in terms of processing-, electrical-, thermal-, and mechanical perspective. Today’s high-performance ICs have on-chip back-end-of-line (BEOL) layers that consist of copper traces and vias interspersed with low-k dielectric materials. These layers have thicknesses in the range of 100 nm near the transistors and 1000 nm away from the transistors close to the solder bumps. In such BEOL layered stacks, cracking and/or delamination is a common failure mode due to the low mechanical and adhesive strength of the dielectric materials as well as due to high thermally-induced stresses. However, there are no available cohesive zone models and parameters to study such interfacial cracks in sub-micron thick microelectronic layers. This work focuses on developing framework based on cohesive zone modeling approach to study interfacial delamination in sub-micron thick layers. Such a framework is then successfully applied to predict microelectronic device reliability. As intentionally creating pre-fabricated cracks in such interfaces is difficult, this work examines a combination of four-point bend and double-cantilever beam tests to create initial cracks and to develop cohesive zone parameters over a range of mode-mixity. Similarly, a combination of four-point bend and end-notch flexure tests is used to cover additional range of mode-mixity. In these tests, silicon wafers obtained from wafer foundry are used for experimental characterization. The developed parameters are then used in actual microelectronic device to predict the onset and propagation of crack, and the results from such predictions are successfully validated with experimental data. In addition, nanoindenter-based shear test technique designed specifically for this study is demonstrated. The new test technique can address different mode mixities compared to the other interfacial fracture characterization tests, is sensitive to capture the change in fracture parameter due to changes in local trace pattern variations around the vicinity of bump and the test mimics the forces experienced by the bump during flip-chip assembly reflow process. Through this experimental and theoretical modeling research, guidelines are also developed for the reliable design of BEOL stacks for current and next-generation microelectronic devices.

The objective of the proposed research is to design, implement, and characterize low-cost, lightweight front-end components and subsystems in the microwave domain through innovative packaging architectures for remote sensing applications. Particular emphasis is placed on system-on-package (SoP) solutions implemented in organic substrates as a low-cost alternative to conventional, expensive, rigid, and fragile radio- frequency substrates. To this end, the dielectric properties of organic substrates RT/duroid 5880, 6002 and 6202 are presented from 30 GHz to 70 GHz, covering most of the Ka and V radar bands, giving also a thorough insight on the uncertainty of the microstrip ring resonator method by means of the Monte Carlo uncertainty analysis. Additionally, an ultra-thin, high-power antenna-array technology, with transmit/ receive (T/R) functionality is introduced for mobile applications in the X band. Two lightweight SoP T/R array panels are presented in this work using novel technologies such as Silicon Germanium integrated circuits and microelectromechanical system switches on a hybrid organic package of liquid crystal polymer and RT/duroid 5880LZ. A maximum power of 47 dBm is achieved in a package with a thickness of 1.8 mm without the need of bulky thermal management devices. Finally, to address the thermal limitations of thin-film substrates of interest (liquid crystal polymer, RT/duroid 6002, alumina and Aluminum Nitride), a thermal assessment of microstrip structures is presented in the X band, along with the thermal characterization of the dielectric properties of RT/duroid 6002 from 20 C to 200 C and from 30 GHz to 70 GHz. Additional high-power, X-band technologies presented in this work include: a novel and compact topology for evanescent mode filters, and low-profile Wilkinson power dividers implemented on Aluminum Nitride using Tantalum Nitride thin-film resistors.

Breast cancer is the second leading cause of death due to cancer in women. A number of effective therapeutic strategies have been implemented in clinics to cope with the disease yet recurrent disease and toxicity reduce their effectiveness. Hence, there is a need to identify and develop more effective therapies with reduced toxic side effects to improve overall survival rates. This dissertation investigates the mechanisms of action of two natural forms of vitamin E and a cholesterol lowering drug, simvastatin, as a therapeutic strategy in human breast cancer cells. Vitamin E in nature consists of eight distinct forms which are fat soluble small lipids. Until recently, vitamin E was known as a potent antioxidant but emerging work suggests they may be resourceful agents in managing a number of chronic diseases including cancer. Anticancer properties of vitamin E have been identified to be limited to the γ- and δ- forms of both tocopherols and tocotrienols. Gamma-tocopherol ([gamma]T) and gamma-tocotrienol ([gamma]T3) have both already been identified to induce death receptor 5 (DR5) mediated apoptosis in breast cancer cells. Studies here show that similar to [gamma]T3, [gamma]T induced DR5 activation is mediated by c-Jun N-terminal kinase/C/EBP homologous protein (JNK/CHOP) proapoptotic axis which in part contributed to [gamma]T mediated dowregulation of c-FLIP, Bcl-2 and Survivin. Also, both agents activate de novo ceramide synthesis pathway which induces JNK/CHOP/DR5 proapoptotic axis and downregulates antiapoptotic factors FLICE inhibitory protein (c-FLIP), B-cell lymphoma 2 (Bcl-2) and Survivin leading to apoptosis. Simvastatin (SVA) has been identified to display pleiotropic effects including anticancer effects but mechanisms responsible for these actions have yet to be fully understood. In this dissertation, it was observed that simvastatin induced apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 proapoptotic axis and down regulation of antiapoptotic factors c-FLIP and Survivin which are in part dependent on JNK/CHOP/DR5 axis. The anticancer effects mediated by simvastatin can be reversed by exogenously added mevalonate and geranylgeranyl pyrophosphate (GGPP), implicating the blockage of mevalonate as a key event. Furthermore, work has been done to understand the factors responsible for drug resistance and identify therapeutic strategies to counteract the same. It was observed that development of drug resistance was associated with an increase in the percentage of tumor initiating cells (TICs) in both tamoxifen and Adriamycin resistant cells compared to their parental counterparts which was accompanied by an increase in phosphorylated form of Signal transducer and activator of transcription 3 (Stat3) proteins as well as its downstream mediators c-Myc, cyclin D1, Bcl-xL and Survivin. Inhibition of Stat3 demonstrated that Stat3 and its downstream mediators play an important role in regulation of TICs in drug resistant breast cancer. Moreover, SVA, [gamma]T3 and combination of SVA+[gamma]T3 has been observed to target TICs in drug resistant human breast cancer cells and downregulate Stat3 as well as its downstream mediators making it an attractive agent to overcome drug resistance. From the data presented here, the mechanisms responsible for the anticancer actions of [gamma]T, [gamma]T3 and SVA have been better understood, providing the necessary rationale to test these agents by themselves or in combination in pre-clinical models. / text

This thesis presents the analysis, design and characterization of an integrated high-frequency phase-locked loop (PLL) frequency multiplier. The frequency multiplier is novel in its use of a low multiplication factor of 4 and a fully differential topology for rejection of common mode interference signals. The PLL is composed of a voltage controlled oscillator (VCO), injection-locked frequency divider (ILFD) for the first divide-by-two stage, a static master-slave flip-flop (MSFF) divider for the second divide-by-two stage and a Gilbert cell mixer phase detector (PD). The circuit has been fabricated using a standard CMOS 0.18-um process based on its relatively low cost and ready availability. The PLL frequency multiplier generates an output signal at 26 GHz and is the highest operational frequency PLL in the technology node reported to date. Time domain phase plane analysis is used for prediction of PLL locking range based on initial conditions of phase and frequency offsets. Tracking range of the PLL is limited by the inherent narrow locking range of the ILFD, and is confirmed via experimental results. The performance benefits of the fully differential PLL are experimentally confirmed by the injection of differential- and common-mode interfering signals at the VCO control lines. A comparison of the common- and differential-mode modulation indices reveals that a common mode rejection ratio (CMRR) of greater than 20 dB is possible for carrier offset frequencies of less than 1 MHz. Closed-loop frequency domain transfer functions are used for prediction of the PLL phase noise response, with the PLL being dominated by the reference and VCO phase noise contributions. Regions of dominant phase noise contributions are presented and correlated to the overall PLL phase noise performance. Experimental verifications display good agreement and confirm the usefulness of the techniques for PLL performance prediction. The PLL clock multiplier has an operational output frequency of 26.204 to 26.796 GHz and a maximum output frequency step of 16 MHz. Measured phase noise at 1 MHz offset from the carrier is -103.9 dBc/Hz. The PLL clock multiplier core circuit (VCO/ILFD/MSFF Divider/PD) consumes 186 mW of combined power from 2.8 and 4.3 V DC rails. / Thesis (Ph.D, Electrical & Computer Engineering) -- Queen's University, 2009-04-24 11:31:35.384

In the first part of the thesis, the molecular structure and electronic properties of phospholipids at the single molecule level and also for a monolayer structure are investigated via ab initio calculations under different degrees of hydration. The focus of the study is on phosphatidylcholines, in particular dipalmitoylphosphatidylcholine (DPPC), which are the most abundant phospholipids in biological membranes. Upon hydration, the phospholipid shape into a sickle-like structure. The hydration dramatically alters the surface potential, dipole and quadrupole moments of the lipids, and probably guides the interactions of the lipids with other molecules and the communication between cells. The vibrational spectrum of DPPC and DPPC-water complexes are completely assigned and it is shown that water hydrating the lipid head groups enables efficient energy transfer across membrane leaflets on sub-picosecond time scales. Moreover, the vibrational modes and lifetimes of pure and hydrated DPPC lipids, at human body temperature, are estimated by performing ab initio molecular dynamics simulations. The vibrational modes of the water molecules close to the head group of DPPC are active in the frequency range between 0.5 - 55 THz, with a peak at 2.80 THz in the energy spectrum. The computed lifetimes for the high-frequency modes agree well with recent data measured at room temperature, where high-order phonon scattering is not negligible. The structure and auto-ionization of water at the water-phospholipid interface are investigated by ab initio molecular dynamics and ab initio Monte Carlo simulations using local density approximation and generalized gradient approximation for the exchange-correlation energy functional. Depending on the lipid head group, strongly enhanced ionization is observed, leading to dissociation of several water molecules into H+ and OH- per lipid. The results can shed light on the phenomena of the high proton conductivity along membranes that has been reported experimentally. In the second part of the thesis, Monte Carlo simulations of the lipid bilayer, on the basis of a coarse grained model, are performed to gain insight into the mechanical properties of planar lipid bilayers. By using a rescaling method, the Poisson's ratio is calculated for different phases. Additional information on the bending rigidity, determined from height fluctuations on the basis of the Helfrich Hamiltonian, allows for calculation of the Young's modulus for each phase. In addition, the free energy barrier for lipid flip-flop process in the fluid and gel phases are estimated. The main rate-limiting step to complete a flip-flop process is related to a free energy barrier that has to be crossed in order to reach the center of the bilayer. The free energy cost for performing a lipid flip-flop in the gel phase is found to be five times greater than in the fluid phase, demonstrating the rarity of such events in the gel phase. Moreover, an energy barrier is estimated for formation of transient water pores that often precedes lipid translocation events and accounts for the rate-limiting step of these pore-associated lipid translocation processes.

Indiana University-Purdue University Indianapolis (IUPUI) / Blömmer, Otto, and Seifert presented a fault attack on elliptic curve scalar multiplication called the Sign Change Attack, which causes a fault that changes the sign of the accumulation point. As the use of a sign bit for an extended integer is highly unlikely, this appears to be a highly selective manipulation of the key stream. In this thesis we describe two plausible fault attacks on a smart card implementation of elliptic curve cryptography. King and Wang designed a new attack called counter fault attack by attacking the scalar multiple of discrete-log cryptosystem. They then successfully generalize this approach to a family of attacks. By implementing King and Wang's scheme on RSA, we successfully attacked RSA keys for a variety of sizes. Further, we generalized the attack model to an attack on any implementation that uses NAF and wNAF key.