Design and Synthesis of Acridine-Based Macrocyclic G-Quadruplex DNA Ligands

DNA sequences that are rich in the guanine nucleic base possess the ability to fold into higher order structures called G-quadruplexes. These higher level structures are formed as a result of two sets of four guanine bases hydrogen-bonding together in a planar arrangement called a guanine quartet. Guanine quartets subsequently stack upon each other to form quadruplexes. G-quadruplexes are mainly localized in telomeres as well as in oncogene promoters. One unique and promising therapeutic approach against cancer involves targeting and stabilizing G-quadruplexes with small molecules, generally in order to suppress oncogene expression and telomerase enzyme activity; the latter has been found to contribute to “out-of control” cell growth in ca. 80-85% of all cancer cells and primary tumours while being absent in normal somatic cells. In this work, we present efforts towards designing and synthesizing acridine-based macrocycles (Mh) and (Mb) with the purpose of providing potential G4 ligands that are suited for selective binding to G4 vs. duplex DNA, and stabilize G-quadruplex structures. Two ligands described in this study include an acridine core which provides an aromatic surface capable of π-π interactions with the surface of G-quadruplexes. The successful synthesis of 4,5-diaminoacridine is described in chapter 2, as an essential fragment of the macrocycles (Mh) and (Mb). In order to investigate the synthetic method for macrocyclization, model compounds composing almost half of the designed macrocycles were explored. As discussed in chapter 3, the synthesis of the model compound for (Mb) turned out to be challenging. However, as a step towards the synthesis of (Mh), the synthesis of the hydrogen-containing model compound, which is almost half of the desired macrocycle (Mh) was achieved in our group and proved to be promising.

Advances in single-shot, dry drilling of composite/metal stacks

Carbon fibre reinforced polymers (CFRP) are increasingly being used in the aerospace, automotive and defence industry due to their high specific stiffness and good corrosion resistance. In a modern aircraft, 50-60% of its structure is made up of CFRP material while the remainder is mostly a combination of metallic alloys (typically aluminium or titanium alloys). Mechanical fastening (bolting or riveting) of CFRP and metallic components has thus created a pressing requirement of drilling several thousand holes per aircraft. Drilling of stacks in a single-shot not only saves time, but also ensures proper alignment when fasteners are inserted, achieving tighter geometric tolerances. However, this requirement poses formidable manufacturing challenges due to the fundamental differences in the material properties of CFRP and metals e.g. a drill bit entering into the stack encounters brittle and abrasive CFRP material as well as the plastic behaviour of the metallic alloy, making the drilling process highly non-linear.

Over the past few years substantial efforts have been made in this direction and majority of the research has tried to establish links between how the process parameters (feed, depth of cut, cutting speed), tooling (geometry, material and coating) and the wear of the cutting tool affect the hole quality. Similarly, multitudes of investigations have been conducted to determine the effects of non-traditional drilling methods (orbital, helical and vibration assisted drilling), cutting zone temperatures and efficiency of chip extraction on the hole quality and rate of tool wear during single shot drilling of CFRP/alloy stacks.

In a timely effort, this paper aims at reviewing the manufacturing challenges and barriers faced when drilling CFRP/alloy stacks and to summarise various factors influencing the drilling process while detailing the advances made in this fertile research area of single-shot drilling of stack materials. A survey of the key challenges associated with avoiding workpiece damage and the effect these challenges have on tool design and process optimisation is presented. An in depth critique of suitable hole making methods and their aptness for commercialisation follows. The paper concludes by summarising the future work required to achieve repeatable, high quality single shot drilled holes in CFRP/alloy stacks.

Lacustrine Arcellinina (Testate Amoebae) as Bioindicators of Arsenic Contamination

Arcellininids (testate amoebae) were examined from 61 surface sediment samples collected from 59 lakes in the vicinity of former gold mines, notably Giant Mine, near Yellowknife, Northwest Territories, Canada to determine their utility as bioindicators of arsenic (As), which occurs both as a byproduct of gold extraction at mines in the area and ore-bearing outcrops. Cluster analysis (Q-R-mode) and detrended correspondence analysis (DCA) reveal five arcellininid assemblages, three of which are related to varying As concentrations in the sediment samples. Redundancy analysis (RDA) showed that 14 statistically significant environmental parameters explained 57 % of the variation in faunal distribution, while partial RDA indicated that As had the greatest influence on assemblage variance (10.7 %; p < 0.10). Stress-indicating species (primarily centropyxids) characterized the faunas of samples with high As concentrations (median = 121.7 ppm, max > 10000 ppm, min = 16.1 ppm, n = 32), while difflugiid dominated assemblages were prevalent in substrates with relatively low As concentrations (median = 30.2 ppm, max = 905.2 ppm, min = 6.3 ppm, n = 20). Most of the lakes with very high As levels are located downwind (N and W) of the former Giant Mine roaster stack where refractory ore was roasted and substantial quantities of As were released (as As2O3) to the atmosphere in the first decade of mining. This spatial pattern suggests that a significant proportion of the observed As, in at least these lakes, are industrially derived. The results of this study highlight the sensitivity of Arcellinina to As and confirm that the group has considerable potential for assessing the impact of As contamination on lakes.

Searching for swept-up hydrogen and helium in the late-time spectra of 11 nearby Type Ia supernovae

The direct detection of a stellar system that explodes as a Type Ia supernova (SN Ia) has not yet been successful. Various indirect methods have been used to investigate SN Ia progenitor systems but none have produced conclusive results. A prediction of single-degenerate models is that H- (or He-) rich material from the envelope of the companion star should be swept up by the SN ejecta in the explosion. Seven SNe Ia have been analysed to date looking for signs of H-rich material in their late-time spectra and none were detected. We present results from new late-time spectra of 11 SNe Ia obtained at the Very Large Telescope using XShooter and FORS2. We present the tentative detection of Hα emission for SN 2013ct, corresponding to ∼0.007 M_⊙ of stripped/ablated companion star material (under the assumptions of the spectral modelling). This mass is significantly lower than expected for single-degenerate scenarios, suggesting that >0.1 M_⊙ of H-rich is present but not observed. We do not detect Hα emission in the other 10 SNe Ia. This brings the total sample of normal SNe Ia with non-detections (<0.001–0.058 M_⊙) of H-rich material to 17 events. The simplest explanation for these non-detections is that these objects did not result from the explosion of a CO white dwarf accreting matter from a H-rich companion star via Roche lobe overflow or symbiotic channels. However, further spectral modelling is needed to confirm this. We also find no evidence of He-emission features, but models with He-rich companion stars are not available to place mass limits.

BIORETENTION/CISTERN/IRRIGATION TO ELIMINATE STORMWATER RUNOFF AT THE UNIVERSITY OF MARYLAND

Water quality of parking lot (~1,858 m2) stormwater runoff and its treated effluent flow were analyzed for total phosphorus (TP), total nitrogen (TN), total suspended solids (TSS), electrical conductivity (EC), copper, lead and zinc. The novel system under investigation, located at the University of Maryland, College Park, Maryland, includes a standard bioretention facility, underdrained to a cistern to store treated stormwater, and pumped to a vegetable garden for irrigation. The site abstraction, the average bioretention abstraction, and bowl volumes were estimated to be 8500, 4378, and 895 L, respectively; this indicates that rain events of more than 0.45 cm are necessary to produce runoff and more than 0.75 cm will produce system overflow. The cistern water quality indicates good-to-excellent treatment by the system. Compared to local tap water, cistern water has lower concentrations of TP, TN, EC (non-winter), copper, and zinc, indicating a good water source for irrigation.

Electrical and optical studies on carbon nanotube arrays

Single-walled carbon nanotubes (SWNTs) have been studied as a prominent class of high performance electronic materials for next generation electronics. Their geometry dependent electronic structure, ballistic transport and low power dissipation due to quasi one dimensional transport, and their capability of carrying high current densities are some of the main reasons for the optimistic expectations on SWNTs. However, device applications of individual SWNTs have been hindered by uncontrolled variations in characteristics and lack of scalable methods to integrate SWNTs into electronic devices. One relatively new direction in SWNT electronics, which avoids these issues, is using arrays of SWNTs, where the ensemble average may provide uniformity from device to device, and this new breed of electronic material can be integrated into electronic devices in a scalable fashion. This dissertation describes (1) methods for characterization of SWNT arrays, (2) how the electrical transport in these two-dimensional arrays depend on length scales and spatial anisotropy, (3) the interaction of aligned SWNTs with the underlying substrate, and (4) methods for scalable integration of SWNT arrays into electronic devices. The electrical characterization of SWNT arrays have been realized by polymer electrolyte-gated SWNT thin film transistors (TFTs). Polymer electrolyte-gating addresses many technical difficulties inherent to electrical characterization by gating through oxide-dielectrics. Having shown polymer electrolyte-gating can be successfully applied on SWNT arrays, we have studied the length scaling dependence of electrical transport in SWNT arrays. Ultrathin films formed by sub-monolayer surface coverage of SWNT arrays are very interesting systems in terms of the physics of two-dimensional electronic transport. We have observed that they behave qualitatively different than the classical conducting films, which obey the Ohm’s law. The resistance of an ultrathin film of SWNT arrays is indeed non-linear with the length of the film, across which the transport occurs. More interestingly, a transition between conducting and insulating states is observed at a critical surface coverage, which is called percolation limit. The surface coverage of conducting SWNTs can be manipulated by turning on and off the semiconductors in the SWNT array, leading to the operation principle of SWNT TFTs. The percolation limit depends also on the length and the spatial orientation of SWNTs. We have also observed that the percolation limit increases abruptly for aligned arrays of SWNTs, which are grown on single crystal quartz substrates. In this dissertation, we also compare our experimental results with a two-dimensional stick network model, which gives a good qualitative picture of the electrical transport in SWNT arrays in terms of surface coverage, length scaling, and spatial orientation, and briefly discuss the validity of this model. However, the electronic properties of SWNT arrays are not only determined by geometrical arguments. The contact resistances at the nanotube-nanotube and nanotube-electrode (bulk metal) interfaces, and interactions with the local chemical groups and the underlying substrates are among other issues related to the electronic transport in SWNT arrays. Different aspects of these factors have been studied in detail by many groups. In fact, I have also included a brief discussion about electron injection onto semiconducting SWNTs by polymer dopants. On the other hand, we have compared the substrate-SWNT interactions for isotropic (in two dimensions) arrays of SWNTs grown on Si/SiO2 substrates and horizontally (on substrate) aligned arrays of SWNTs grown on single crystal quartz substrates. The anisotropic interactions associated with the quartz lattice between quartz and SWNTs that allow near perfect horizontal alignment on substrate along a particular crystallographic direction is examined by Raman spectroscopy, and shown to lead to uniaxial compressive strain in as-grown SWNTs on single crystal quartz. This is the first experimental demonstration of the hard-to-achieve uniaxial compression of SWNTs. Temperature dependence of Raman G-band spectra along the length of individual nanotubes reveals that the compressive strain is non-uniform and can be larger than 1% locally at room temperature. Effects of device fabrication steps on the non-uniform strain are also examined and implications on electrical performance are discussed. Based on our findings, there are discussions about device performances and designs included in this dissertation. The channel length dependences of device mobilities and on/off ratios are included for SWNT TFTs. Time response of polymer-electrolyte gated SWNT TFTs has been measured to be ~300 Hz, and a proof-of-concept logic inverter has been fabricated by using polymer electrolyte gated SWNT TFTs for macroelectronic applications. Finally, I dedicated a chapter on scalable device designs based on aligned arrays of SWNTs, including a design for SWNT memory devices.

Compiling Exceptions Correctly

Exceptions are an important feature of modern programming languages, but their compilation has traditionally been viewed as an advanced topic. In this article we show that the basic method of compiling exceptions using stack unwinding can be explained and verified both simply and precisely, using elementary functional programming techniques. In particular, we develop a compiler for a small language with exceptions, together with a proof of its correctness.

Structure, transports and transformations of the water masses in the Atlantic Subpolar Gyre

We discuss the distributions and transports of the main water masses in the North Atlantic Subpolar Gyre (NASPG) for the mean of the period 2002–2010 (OVIDE sections 2002–2010 every other year), as well as the inter-annual variability of the water mass structure from 1997 (4x and METEOR sections) to 2010. The water mass structure of the NASPG, quantitatively assessed by means of an Optimum MultiParameter analysis (with 14 water masses), was combined with the velocity fields resulting from previous studies using inverse models to obtain the water mass volume transports. We also evaluate the relative contribution to the Atlantic Meridional Overturning Circulation (AMOC) of the main water masses characterizing the NASPG, identifying the water masses that contribute to the AMOC variability. The reduction of the magnitude of the upper limb of the AMOC between 1997 and the 2000s is associated with the reduction in the northward transport of the Central Waters. This reduction of the northward flow of the AMOC is partially compensated by the reduction of the southward flow of the lower limb of the AMOC, associated with the decrease in the transports of Polar Intermediate Water and Subpolar Mode Water (SPMW) in the Irminger Basin. We also decompose the flow over the Reykjanes Ridge from the East North Atlantic Basin to the Irminger Basin (9.4 ± 4.7 Sv) into the contributions of the Central Waters (2.1 ± 1.8 Sv), Labrador Sea Water (LSW, 2.4 ± 2.0 Sv), Subarctic Intermediate Water (SAIW, 4.0 ± 0.5 Sv) and Iceland–Scotland Overflow Water (ISOW, 0.9 ± 0.9 Sv). Once LSW and ISOW cross over the Reykjanes Ridge, favoured by the strong mixing around it, they leave the Irminger Basin through the deep-to-bottom levels. The results also give insights into the water mass transformations within the NASPG, such as the contribution of the Central Waters and SAIW to the formation of the different varieties of SPMW due to air–sea interaction.

THE PHYSICS OF IDEAS: INFERRING THE MECHANICS OF OPINION FORMATION FROM MACROSCOPIC STATISTICAL PATTERNS

In a microscopic setting, humans behave in rich and unexpected ways. In a macroscopic setting, however, distinctive patterns of group behavior emerge, leading statistical physicists to search for an underlying mechanism. The aim of this dissertation is to analyze the macroscopic patterns of competing ideas in order to discern the mechanics of how group opinions form at the microscopic level. First, we explore the competition of answers in online Q&A (question and answer) boards. We find that a simple individual-level model can capture important features of user behavior, especially as the number of answers to a question grows. Our model further suggests that the wisdom of crowds may be constrained by information overload, in which users are unable to thoroughly evaluate each answer and therefore tend to use heuristics to pick what they believe is the best answer. Next, we explore models of opinion spread among voters to explain observed universal statistical patterns such as rescaled vote distributions and logarithmic vote correlations. We introduce a simple model that can explain both properties, as well as why it takes so long for large groups to reach consensus. An important feature of the model that facilitates agreement with data is that individuals become more stubborn (unwilling to change their opinion) over time. Finally, we explore potential underlying mechanisms for opinion formation in juries, by comparing data to various types of models. We find that different null hypotheses in which jurors do not interact when reaching a decision are in strong disagreement with data compared to a simple interaction model. These findings provide conceptual and mechanistic support for previous work that has found mutual influence can play a large role in group decisions. In addition, by matching our models to data, we are able to infer the time scales over which individuals change their opinions for different jury contexts. We find that these values increase as a function of the trial time, suggesting that jurors and judicial panels exhibit a kind of stubbornness similar to what we include in our model of voting behavior.

In situ characterization of sediment oxygen demand across the spectrum of non-resuspension to full resuspension with varying bed shear stress

Sediment oxygen demand (SOD) can be a significant oxygen sink in various types of water bodies, particularly slow-moving waters with substantial organic sediment accumulation. In most settings where SOD is a concern, the prevailing hydraulic conditions are such that the impact of sediment resuspension on SOD is not considered. However, in the case of Bubbly Creek in Chicago, Illinois, the prevailing slack water conditions are interrupted by infrequent intervals of very high flow rates associated with pumped combined sewer overflow (CSO) during intense hydrologic events. These events can cause resuspension of the highly organic, nutrient-rich bottom sediments, resulting in precipitous drawdown of dissolved oxygen (DO) in the water column. While many past studies have addressed the dependence of SOD on near-bed velocity and bed shear stress prior to the point of sediment resuspension, there has been limited research that has attempted to characterize the complex and dynamic phenomenon of resuspended-sediment oxygen demand. To address this issue, a new in situ experimental apparatus referred to as the U of I Hydrodynamic SOD Sampler was designed to achieve a broad range of velocities and associated bed shear stresses. This allowed SOD to be analyzed across the spectrum of no sediment resuspension associated with low velocity/ bed shear stress through full sediment resuspension associated with high velocity / bed shear stress. The current study split SOD into two separate components: (1) SODNR is the sediment oxygen demand associated with non-resuspension conditions and is a surface sink calculated using traditional methods to yield a value with units (g/m2/day); and (2) SODR is the oxygen demand associated with resuspension conditions, which is a volumetric sink most accurately characterized using non-traditional methods and units that reflect suspension in the water column (mg/L/day). In the case of resuspension, the suspended sediment concentration was analyzed as a function of bed shear stress, and a formulation was developed to characterize SODR as a function of suspended sediment concentration in a form similar to first-order biochemical oxygen demand (BOD) kinetics with Monod DO term. The results obtained are intended to be implemented into a numerical model containing hydrodynamic, sediment transport, and water quality components to yield oxygen demand varying in both space and time for specific flow events. Such implementation will allow evaluation of proposed Bubbly Creek water quality improvement alternatives which take into account the impact of SOD under various flow conditions. Although the findings were based on experiments specific to the conditions in Bubbly Creek, the techniques and formulations developed in this study should be applicable to similar sites.

Measurement of target single-spin asymmetry in charged kaon electroproduction on a transversely polarized 3He target

The subject of quark transverse spin and transverse momentum distribution are two current research frontier in understanding the spin structure of the nucleons. The goal of the research reported in this dissertation is to extract new information on the quark transversity distribution and the novel transverse-momentum-dependent Sivers function in the neutron. A semi-inclusive deep inelastic scattering experiment was performed at the Hall A of the Jefferson laboratory using 5.9 GeV electron beam and a transversely polarized ^{3}He target. The scattered electrons and the produced hadrons (pions, kaons, and protons) were detected in coincidence with two large magnetic spectrometers. By regularly flipping the spin direction of the transversely polarized target, the single-spin-asymmetry (SSA) of the semi-inclusive deep inelastic reaction ^{3}He^{uparrow}(e,e'h^{\pm})X was measured over the kinematic range 0.13 < x < 0.41 and 1.3 < Q^{2} < 3.1 (GeV)^{2}. The SSA contains several different azimuthal angular modulations which are convolutions of quarks distribution functions in the nucleons and the quark fragmentation functions into hadrons. It is from the extraction of the various ``moments'' of these azimuthal angular distributions (Collins moment and Sivers moment) that we obtain information on the quark transversity distribution and the novel T-odd Sivers function. In this dissertation, I first introduced the theoretical background and experimental status of nucleon spins and the physics of SSA. I will then present the experimental setup and data collection of the JLab E06-010 experiment. Details of data analysis will be discussed next with emphasis on the kaon particle identification and the Ring-Imaging Cherenkov detector which are my major responsibilities in this experiment. Finally, results on the kaon Collins and Sivers moments extracted from the Maximum Likelihood method will be presented and interpreted. I will conclude with a discussion on the future prospects for this research.

The development of planar high-K/III-V p-channel MOSFETs for post-silicon CMOS

Conventional Si complementary-metal-oxide-semiconductor (CMOS) scaling is fast approaching its limits. The extension of the logic device roadmap for future enhancements in transistor performance requires non-Si materials and new device architectures. III-V materials, due to their superior electron transport properties, are well poised to replace Si as the channel material beyond the 10nm technology node to mitigate the performance loss of Si transistors from further reductions in supply voltage to minimise power dissipation in logic circuits. However several key challenges, including a high quality dielectric/III-V gate stack, a low-resistance source/drain (S/D) technology, heterointegration onto a Si platform and a viable III-V p-metal-oxide-semiconductor field-effect-transistor (MOSFET), need to be addressed before III-Vs can be employed in CMOS. This Thesis specifically addressed the development and demonstration of planar III-V p-MOSFETs, to complement the n-MOSFET, thereby enabling an all III-V CMOS technology to be realised. This work explored the application of InGaAs and InGaSb material systems as the channel, in conjunction with Al2O3/metal gate stacks, for p-MOSFET development based on the buried-channel flatband device architecture. The body of work undertaken comprised material development, process module development and integration into a robust fabrication flow for the demonstration of p-channel devices. The parameter space in the design of the device layer structure, based around the III-V channel/barrier material options of In_x≥0.53Ga_1-xAs/In_0.52Al_0.48As and In_x≥0.1Ga_1-xSb/AlSb, was systematically examined to improve hole channel transport. A mobility of 433 cm²/Vs, the highest room temperature hole mobility of any InGaAs quantum-well channel reported to date, was obtained for the In_0.85Ga_0.15As (2.1% strain) structure. S/D ohmic contacts were developed based on thermally annealed Au/Zn/Au metallisation and validated using transmission line model test structures. The effects of metallisation thickness, diffusion barriers and de-oxidation conditions were examined. Contacts to InGaSb-channel structures were found to be sensitive to de-oxidation conditions. A fabrication process, based on a lithographically-aligned double ohmic patterning approach, was realised for deep submicron gate-to-source/drain gap (L_side) scaling to minimise the access resistance, thereby mitigating the effects of parasitic S/D series resistance on transistor performance. The developed process yielded gaps as small as 20nm. For high-k integration on GaSb, ex-situ ammonium sulphide ((NH₄)₂S) treatments, in the range 1%-22%, for 10min at 295K were systematically explored for improving the electrical properties of the Al₂O₃/GaSb interface. Electrical and physical characterisation indicated the 1% treatment to be most effective with interface trap densities in the range of 4 - 10×10¹²cm^-2eV^-1 in the lower half of the bandgap. An extended study, comprising additional immersion times at each sulphide concentration, was further undertaken to determine the surface roughness and the etching nature of the treatments on GaSb. A number of p-MOSFETs based on III-V-channels with the most promising hole transport and integration of the developed process modules were successfully demonstrated in this work. Although the non-inverted InGaAs-channel devices showed good current modulation and switch-off characteristics, several aspects of performance were non-ideal; depletion-mode operation, modest drive current (I_d,sat=1.14mA/mm), double peaked transconductance (g_m=1.06mS/mm), high subthreshold swing (SS=301mV/dec) and high on-resistance (R_on=845kΩ.μm). Despite demonstrating substantial improvement in the on-state metrics of I_d,sat (11×), g_m (5.5×) and R_on (5.6×), inverted devices did not switch-off. Scaling gate-to-source/drain gap (L_side) from 1μm down to 70nm improved I_d,sat (72.4mA/mm) by a factor of 3.6 and gm (25.8mS/mm) by a factor of 4.1 in inverted InGaAs-channel devices. Well-controlled current modulation and good saturation behaviour was observed for InGaSb-channel devices. In the on-state In_0.3Ga_0.7Sb-channel (I_d,sat=49.4mA/mm, g_m=12.3mS/mm, R_on=31.7kΩ.μm) and In_0.4Ga_0.6Sb-channel (I_d,sat=38mA/mm, g_m=11.9mS/mm, R_on=73.5kΩ.μm) devices outperformed the InGaAs-channel devices. However the devices could not be switched off. These findings indicate that III-V p-MOSFETs based on InGaSb as opposed to InGaAs channels are more suited as the p-channel option for post-Si CMOS.

Electronic Packaging of Paper-Based Anisotropic Magnetoresistive Sensors

This report investigates adaptations of electronic packaging methods used to create stacks of these sensors. Four methods were developed and tested to determine the best option in terms of mechanical stability and electrical conductivity of the system. For the first method, a stack is created by way of through paper vias (TPVs), a hole that is cut in the pads of the sensors and then filled with electrically conductive adhesive through the openings on the two sensors to be joined. The second method is called mechanical caulking and connects sensors through pads which have been lined with copper tape backed with conductive adhesive. The connection is created with a small copper rivet which is flattened in place by compressive force. The third method is the stitching method which is inspired by sewing of fabric. A pattern of thin copper wire is stitched on the pad of a sensor that is lined with copper tape backed with conductive adhesive. The wire is then stitched through a second sensor that is treated similarly with copper tape and the stack receives the same pattern through the two layers as was applied to the first sensor alone. The final method is the collapsed daisy chain which is the linear connection of sensors to their neighboring sensors via copper tape backed with conductive adhesive. The row of sensors is then collapsed in an alternating orientation into a single stack.