Effective design of liquid fuel injection systems is a function of good understanding of liquid breakup mechanisms. A transient liquid breakup model is developed on the classical interfacial breakup theory by modifying the classical linear perturbation process to include time-dependent base and perturbed flow parameters. The non-isothermal condition on liquid jet instability and breakup is theoretically modelled; with the particular consideration of a spatially variation of surface tension along the liquid-gas interface. The model combines the classical interface hydrodynamic instability and breakup theory and heat-transfer through semi-infinite medium. Analytical liquid breakup model, which combines transient and non-isothermal effects on liquid jet breakup, is suggested. The suggested model could be simplified to the transient breakup model and the non-isothermal breakup model equivalents. A novel mechanistic model, which is based on a simple momentum balance between the injected jet and the aerodynamic drag force, is suggested for breakup length. A new model, which combines energy criterion and dual-timescale for turbulent shear in droplet dispersion, is suggested for droplet breakup criteria on the basis of critical Webber number. All developed models showed good predictions of available experimental data, and established empirical correlation, within the operational conditions of contemporary ICEs, specifically diesel engines. Continued research in these areas could benefit the development of the next generation of liquid fuel injectors and combustors – by accounting for transient effects and non-isothermal conditions in liquid jet breakup, and turbulent shear in droplet breakup.

This work studies the effects of radial flow on the aerodynamic phenomena occurring on a retreating blade with a focus on dynamic stall and reverse flow as applied to both a helicopter rotor in forward flight and a wind turbine operating at a yaw angle. While great progress has been made in understanding the phenomenon of two-dimensional dynamic stall, the effect of rotation on the dynamic stall event is not well understood. Experiments were conducted on a rigid two bladed teetering rotor at high advance ratios in a low speed wind tunnel. Particle image velocimetry (PIV) measurements were used to quantify the flow field at several azimuthal angles on the rotating blade during the dynamic stall event. The effect of centrifugal forces induced ``pure'' radial velocity on the dynamic stall event at 270 degrees azimuth was studied in detail. Further investigation of the radial flow field suggested that the mean radial velocity attenuated on moving outboard due to an apparent shear layer instability and it was demonstrated to be of first order importance in the flow field. These radial flow results prompted an exploration of the flow over a rotating disk to establish similarities of the radial flow over rotating blade in separated flow to that over a rotating disk in separated flow. While a greater part of this work focused on aspects of dynamic stall on the retreating blade, the final parts focus on the exotic flow regime of reverse flow (characterized by flow from the trailing edge to the leading edge of the blade). Aerodynamic loads measurement and surface flow visualization via tufts are used to first quantify the behavior of a static yawed blade in reverse flow. PIV measurements are then used on a static yawed blade and a rotating blade in reverse flow conditions to ascertain the effects of rotation on reverse flow.

Fanconi anemia (FA) is a genome instability syndrome that is clinically manifested by bone marrow failure, congenital defects, and elevated cancer susceptibility. The FA pathway is known to regulate the repair of DNA interstrand crosslinks in part through DNA homologous recombination (HR) repair. Up to today 16 FA proteins have been discovered that may participate in the common pathway. Cells that have mutations in the FA genes are hypersensitive to DNA damaging agents and display chromosome instability. A key regulatory event in the FA pathway is monoubiquitination of FANCD2-FANCI heterodimer that is mediated by a multi-component E3 ubiquitin ligase complex called FA core complex. Current model suggests that once the FANCD2-FANCI heterodimer is monoubiquitinated it relocates to chromatin where it interacts with other key repair proteins to facilitate DNA repair. More than 90% of the FA cases are presumed to be associated with defects in the monoubiquitination reaction, suggesting the significance of the modification in the pathogenesis of the disease. Despite the significance, the molecular interplay between the FA core complex and the FANCD2-FANCI heterodimer remains enigmatic. We are interested in the assembly mechanism of the various FA subcomplexes into the core complex, and we are actively investigating how the FANCD2-FANCI heterodimer is recruited to these putative subcomplexes. As the FA pathway is a crucial determinant for cellular resistance to DNA damaging agents, there have been hypotheses that disruption of this pathway may be beneficial in enhancing chemosensitivity of certain cancer cells. In collaboration with Dr. Cai’s chemistry lab, we will develop a screen platform to identify a small molecules to interrupt the monoubiquitination reaction. Completion of these studies will enhance the much-needed knowledge of the key enzymatic reaction in the pathway, and perhaps the information can be used for development of novel chemotherapeutic strategies.

This dissertation analyzes changes in the ruling strategies of the Chinese Communist Party (CCP) in the context of economic reforms, beginning in 1978. By employing both quantitative and qualitative methods, this dissertation investigates how Chinese leaders have utilized legitimating strategies, while modifying their governing strategies, in order to a) solidify the population, b) consolidate ruling authority and c) maintain political and social stability. Specifically, this dissertation looks at how Chinese policymakers have developed effective public policies in response to rapidly rising wage inequality, one of the most pressing problems undermining the CCP’s ruling authority. By providing an original estimate of China’s wage inequality and analyzing the government’s response to it, this dissertation provides a unique look at how the CCP has transformed government functions from growth-based to people-centered to meet various social, political and economic challenges. A comparative statistical analysis helps illustrate the philosophical roots and sources of the CCP’s political legitimacy. The technique of Theil Statistics is applied to measure China’s wage inequality during the reform period. A multivariate hierarchical regression analysis is employed to measure the impact of rising inequality on Chinese society. Two models on social welfare system reform are studied in order to understand Hu Jintao and Wen Jiabao’s people-centered governing philosophy and the rationale for constructing a service-oriented government. / text

The stability and turbulence characteristics of a vortex filament emanating from a single-bladed rotor in hover are investigated using proper orthogonal decomposition. The rotor is operated at a tip chord Reynolds number and a tip Mach number of 218,000 and 0.22, respectively, and with a blade loading of CT /σ = 0.066. In-plane components of the velocity field (normal to the axis of the vortex filament) are captured by way of 2D particle image velocimetry with corrections for vortex wander being performed using the Γ1 method. Using the classical form of POD, the first POD mode alone is found to encompass nearly 75% of the energy for all vortex ages studied and is determined using a grid of sufficient resolution as to avoid numerical integration errors in the decomposition. The findings reveal an equal balance between the axisymmetric and helical modes during vortex roll-up which immediately transitions to helical mode dominance at all other vortex ages. This helical mode is one of the modes of the elliptic instability. While the snapshot POD is shown to reveal similar features of the first few energetic modes, the classical POD is employed here owing to the easier interpretation of the Fourier-azimuthal modes. The spatial eigenfunctions of the first few Fourier-azimuthal modes associated with the most energetic POD mode are shown to be sensitive to the choice of the wander correction technique used. Higher Fourier-azimuthal modes are observed in the outer portions of the vortex and appeared not to be affected by the choice of the wander correction technique used. / text

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During every cell cycle and upon exogenous stress, tumor suppression programs are engaged to ensure genomic stability. In response to replicative aging and oncogenic stimuli, the p53 and Rb pathways are activated to prevent the proliferation of damaged cells. Several lines of evidence suggest that escape from senescence is a crucial early step in oncogenic progression. A major challenge in the cancer field is to combine genomic information regarding cancer-associated genetic changes with high-throughput functional studies, in order to confirm genetic requirements and pinpoint biological roles of these perturbed genes in oncogenesis. Furthermore, a complete genetic understanding of replicative senescence, and how it might be bypassed, is lacking. We describe here two genome scale loss-of-function genetic screens that interrogate these tumor suppressor programs. We utilized a unique sensitization approach to isolate senescence pathways and unmask compensatory mechanisms that may have been difficult to identify in previous studies. These genetic screens have generated comprehensive and validated datasets of putative senescence and p53 pathway genes. We present this dataset as a high-quality resource for further investigation into these biological pathways. We have uncovered several genes in distinct biological pathways which have not been demonstrated to have a functional role in senescence, and which may be putative tumor suppressors. We have identified BRD7 and BAF180, two SWI/SNF components, as critical regulators of p53. BRD7 and BAF180 are required for p53 activity and p21 expression during replicative and oncogene-induced senescence, and evidence suggests that they are inactivated in human cancer. In addition, we have uncovered a role for the deubiquitinating enzyme USP28 in the regulation of p53 accumulation during senescence, such that loss of USP28 results in bypass of the senescence program. We have also investigated several other novel senescence genes including SEMA6A, SEMA3b, and TMEM154. We have found that the expression of these genes is highly regulated during senescence by distinct means, including both p53-dependent and p53-independent mechanisms. These results demonstrate the efficacy of our sensitized screening approach, and also highlight the emerging view that the senescence program requires the combined action of multiple biological pathways for its execution.

The National Institute of Mental Health’s (NIMH) Research Domain Criteria (RDoC; Insel et al., 2010; Sanislow et al., 2010) were established in an effort to explore underlying dimensions that cut across many existing disorders as well as to provide an alternative to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5; APA, 2013). The present dissertation aimed to study one major component of the RDoC model, negative valence, as compared to other models hypothesized to be closely related, as well as its relationship to a key component of psychopathology, affective instability. Participants were adult community residents (N=90) currently in mental health treatment. Participants received self-report measures of RDoC negative valence, five-factor model (FFM) neuroticism, and DSM-5 Section 3 negative affectivity, along with measures of affective instability, borderline personality disorder, and social-occupational impairment. Through this investigation, a better understanding and potential expansion of this new model of diagnosis for clinicians and researchers is provided. In particular, it is suggested that RDoC negative valence is commensurate with FFM neuroticism and DSM-5 negative affectivity, and it would be beneficial if it was expanded to include affective instability.

When excavating a rock wall by blasting, pre-existing structures in the rock has a strong impact on the stability of the wall. For excavation in Bandhagen in Stockholm, the nature and orientation of the pre-existing geological features, namely fractures, were not taken into consideration before excavation begun. Geological field studies were carried out in order to investigate the possibility of a more favorable outcome than in the Bandhagen case. Mapping conducted in March 2015 was focused on fracture distribution and the results showed two sets of open shear fractures with fresh surfaces. The first set of the fractures cross-cuts the wall with a strike of NNW-SSE and dips between 70°±30°. The second set of fractures strikes WSW-ENE and are almost parallel to the wall (which strikes roughly 65° E) with a dip towards it, ranging between 55°±35°. The two set of fractures intersect with an acute angle of around 80° and due to their orientation, and that one of the sets dip towards the free face of the wall, they create an unfavorable fracture pattern that makes the wall, at parts, very instable in regard to rockfall and rockslide.  Fractures within the respective sets dip towards opposite cardinal points and making an acute angle of 50° for set 2 and 70° for set 1 fractures within the own set are interpreted to conjugate. In addition, there is a well-developed folded foliation that change in strike from parallel to perpendicular to the excavated wall. The foliation is aligned to the strike of both of the fracture sets. This has enabled fractures to open parallel to the mica-rich layers in the gneiss which further adds to the unfavorable pattern of fractures that creates rhombohedral unstable blocks in the rock mass. Due to the fracture pattern, sliding and rockfall have been frequent and safety measures such as rock bolts and a wire mesh have been installed to increase the security factor for the wall. During mapping, a general fracture pattern was possible to deduce from mapping of solely an unexcavated, vegetated part of the area. It became clearer though together with the excavated surface of the wall. Several pre-blast measures could have been preformed to limit rockfall and sliding of rock after excavation. Line-drilling could have been used when blasting near the contour of the wall to decrease the blast-induced fractures by the more effective venting of the excess explosion gas. This could have decreased the closely spaced blast-induced fractures that have been mapped on both the crest and the body of the wall. Another measure would have been to install pre-blast reinforcements on the crest of the wall, which could have prevented at least two large rockfalls that have occurred.  If the fracture pattern were known before excavation begun and the aforementioned measures would have been considered, the stability of the wall and the first excavation would undoubtedly have been more successful. A proposal for future open face excavations is to thoroughly assess the geological features to, in a preliminary stage of the planning, eliminate the risk for this outcome to occur in the future. / Vid uttag av berg genom sprängning för att skapa en bergvägg har strukturerna i berget en stor betydelse för stabiliteten av väggen. Exempel på strukturer i berggrunden som kan orsaka problem vid uttag av berg är sprickor och då speciellt sprickor som stupar mot väggens teoretiska kontur. Dessa sprickor kan orsaka att hela skivor av berg kan glida från väggen. Om dessa sprickor också korsas av andra sprickor kan de tillsammans bilda kilar som stupar ut mot den fria ytan där utschaktning av berg skett. Kilar som dessa som förekommer på krönet av bergväggen faller ofta ut från väggen och kan vara både farliga för de som utför arbetet samtidigt som de kan göra block runtomkring dem mer instabila.  För en utschaktning av berg i Bandhagen, Stockholm togs inte sprickmönstret in i planeringen inför hur sprängning skulle utföras. Detta ledde till att sprängningen som utfördes orsakade mycket glidningar av block och utfall från krönet. Det har lett till att projektet blivit försenat och budgeten överskridits för att korrigera de misstag som gjorts. Korrigeringarna har varit nödvändiga för att väggen i slutändan ska nå en säkerhetsfaktor som inte kan orsaka några person- eller materialskador i framtiden.  Kartering med fokus på sprickfördelning utfördes i Mars 2015 för att undersöka om sprängningen hade kunnat utföras på ett annorlunda och bättre sätt om sprickmönstret varit känt innan sprängning inleddes. Karteringen visade två korsande spricksystem där ett av spricksystemen stryker parallellt med väggen och även stupar mot den. De två systemen av sprickor bildar block med plan som lutar ut från väggen vilket resulterar i att många utfall av block skett. Med vetskapen om dessa spricksystem, samt övriga sprickor som förekommer i området, hade de utfall av berg som skett kunnat förutsägas och därigenom hade förslag av sprängmetodik kunnat ges för att minska utfall och för att generellt fått en säkrare vägg redan ifrån början. Både sprängning med tätsöm nära den teoretiska konturen av väggen och förförstärkning av krönet av den teoretiska väggen innan första sprängningen hade kunnat leda till en mycket stabilare vägg. Det hade kunnat leda till att projektet inte blivit försenat och att budgeten för projektet tagit hänsyn till de problem som skulle kunna uppstå.  Ett förslag för uttag av berg för bergsslänter är att de geologiska förhållandena ska undersökas mer noggrant, för att i ett tidigt skede upptäcka liknande strukturer i berget och utifrån dessa eliminera risken för att liknande problem uppstår i framtiden.

With the gradual advance of the state-of-the-art VLSI manufacturing technology into the sub-45nm regime, engineering a reliable, high performance VLSI chip with economically attractive yield in accordance with Moore's law of scaling and integration has become extremely difficult. Some of the most serious challenges that make this task difficult are: a) the delay of a transistor is strongly dependent on process induced mechanical stress around it, b) the reliability of devices is affected by several aging mechanisms like Negative Bias Temperature Instability (NBTI), hot carrier injection (HCI), etc and c) the delay and reliability of any device are strongly related to lithographically drawn geometry of various features on wafer. These three challenges are the main focus of this dissertation. High performance fabrication processes routinely use embedded silicon-germanium (eSiGe) technology that imparts compressive mechanical stress to PMOS devices. In this work, cell level timing models considering flexibility to modulate active area to change mechanical stress, were proposed and exploited to perform timing optimization during circuit placement phase. Analysis of key physical synthesis optimization steps such as gate sizing and repeater insertion was done to understand and exploit mechanical stress to significantly improve delay of interconnect and device dominated circuits. Regarding circuit reliability, the proposed work is focused on reducing the clock skew degradation due to NBTI effect specially due to the use of clock gating technique for achieving low power operation. In addition, we also target the detrimental impact of burn-in testing on NBTI. The problem is identified and a runtime technique to reduce clock skew increase was proposed. For designs with predictable clock gating activities, a zero overhead design time technique was proposed to reduce clock skew increase over time. The concept of using minimum degradation input vector during static burn-in testing is proposed to reduce the impact of burn-in testing on parametric yield. Delay and reliability strongly depend on dimension of various features on the wafer such as gate oxide thickness, channel length and contact position. Increased variability of these dimensions can severely restrict ability to analyze or optimize a design considering mechanical stress and circuit reliability. One key technique to control physical variability is to move towards regular fabrics. However, to make implementation on regular fabrics attractive, high quality physical design tools need to be developed. This dissertation proposes a new circuit placement algorithm to place a design on a structured ASIC platform with strict site and clock constraints and excellent overall wirelength. An algorithm for reducing the clock and leakage power dissipation of a structured ASIC by reducing spine usage is then proposed to allow lower power dissipation of designs implemented using structured ASICs. / text