TRANSIENT AND MECHANICAL PROPERTIES OF POLY(PHTHALALDEHYDE) AND THE VARIABLE FREQUENCY MICROWAVE CURING OF HIGH-PERFORMANCE THERMOSETS

Research presented in this thesis is split into two parts. The first section involves tuning the transient and mechanical properties of poly(phthaldehyde) to form a flexible, liquefiable transient material that can depolymerize upon the flick of a metaphorical switch. Such materials can be useful for devices designed to vanish into their surroundings once used. This application-based research required further understanding of how plasticizer additives work to not only make flexible films in an efficient manner, but how they can also serve to decrease the freezing point of o-phthalaldehyde, poly(phthaldehyde)’s monomer unit, upon degradation such that said devices can effectively disappear. Chapter 1 section 1.1 introduces how poly(phthalaldehyde) works as a transient material, and Chapter 1 section 1.2 describes some important fundamental concepts pertaining to how plasticizers can efficiently provide flexibility to polymers and how they work to reduce poly(phthaldehyde)’s freezing point upon depolymerization. Chapter 2 describes an initial approach used to successfully make flexible poly(phthaldehyde) films, and Chapter 3 describes an improved approach utilizing fundamental principles discussed in Chapter 1 section 1.2. Lastly, challenges regarding flexible poly(phthaldehyde)’s low strength are discussed. The second section involves studying the variable frequency microwave curing of epoxy and cyanate ester resins. Such resins are used for a broad range of applications, including microelectronic packaging, circuit board substrates, lightweighting, high- temperature performance parts, etc. Regardless of the application some thermosets, particularly those that possess a high glass transition temperature, require elevated temperatures above 100°C and cure times above 2 hours for complete cure. Variable frequency microwave heating as an alternative to conventional, thermal heating has been proposed as a method for reducing cure times and temperatures. However, proposed and sometimes conflicting microwave heating phenomena described by scientists and engineers are still not very well understood. Thus, the overarching goal of this section is to better understand and use microwave-heating mechanisms that can be useful in reducing thermoset cure times. This involves using a microwave field’s ability selectively heat reactive species (i.e. a catalyst) at the microscopic level, which can occur when two different materials of dissimilar dielectric parameters are mixed. Chapter 4 briefly summarizes important fundamentals of matter-interactions with microwave electromagnetic fields, and how it pertains to selective heating phenomena. Chapter 5 and 6 describe the microwave curing of high glass transition temperature, homogeneous epoxy and cyanate esters respectively. Chapter 7 describes microwave enhanced curing of cyanate ester resin upon the addition of graphene and reduced graphene oxide, two microwave-absorbing, catalytic fillers. Finally, the problems regarding quantifying selective heating phenomena and dielectric property characterization are described.Ph.D

New concepts in breast cancer genomics and genetics

Massively parallel DNA and RNA sequencing approaches have generated data on thousands of breast cancer genomes. In this review, we consider progress largely from the perspective of new concepts and hypotheses raised so far. These include challenges to the multistep model of breast carcinogenesis and the discovery of new defects in DNA repair through sequence analysis. Issues for functional genomics include the development of strategies to differentiate between mutations that are likely to drive carcinogenesis and bystander background mutations, as well as the importance of mechanistic studies that examine the role of mutations in genes with roles in splicing, histone methylation, and long non-coding RNA function. The application of genome-annotated patient-derived breast cancer xenografts as a potentially more reliable preclinical model is also discussed. Finally, we address the challenge of extracting medical value from genomic data. A weakness of many datasets is inadequate clinical annotation, which hampers the establishment of links between the mutation spectra and the efficacy of drugs or disease phenotypes. Tools such as dGene and the DGIdb are being developed to identify possible druggable mutations, but these programs are a work in progress since extensive molecular pharmacology is required to develop successful ‘genome-forward’ clinical trials. Examples are emerging, however, including targeting HER2 in HER2 mutant breast cancer and mutant ESR1 in ESR1 endocrine refractory luminal-type breast cancer. Finally, the integration of DNA- and RNA-based sequencing studies with mass spectrometry-based peptide sequencing and an unbiased determination of post-translational modifications promises a more complete view of the biochemistry of breast cancer cells and points toward a new discovery horizon in our understanding of the pathophysiology of this complex disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0460-4) contains supplementary material, which is available to authorized users

Residential area sociodemographic and breast cancer screening venue location built environmental features associated with women’s use of closest venue in greater Sydney, Australia

Understanding environmental predictors of women’s use of closest breast screening venue versus other site(s) may assist optimal venue placement. This study assessed relationships between residential-area sociodemographic measures, venue location features, and women’s use of closest versus other venues. Data of 320,672 Greater Sydney screening attendees were spatially joined to residential state suburbs (SSCs) (n = 799). SSC-level sociodemographic measures included proportions of: women speaking English at home; university-educated; full-time employed; and dwellings with motor-vehicles. A geographic information system identified each woman’s closest venue to home, and venue co-location with bus-stop, train-station, hospital, general practitioner, and shop(s). Multilevel logistic models estimated associations between environmental measures and closest venue attendance. Attendance at closest venue was 59.4%. Closest venue attendance was positively associated with SSC-level women speaking English but inversely associated with SSC-level women university-educated, full-time employed, and dwellings with motor-vehicles. Mobile venue co-location with general practitioner and shop was positively, but co-location with bus-stop and hospital was inversely associated with attendance. Attendance was positively associated with fixed venue co-location with train-station and hospital but inversely associated with venue co-location with bus-stop, general practitioner, and shop. Program planners should consider these features when optimising service locations to enhance utilisation. Some counterintuitive results necessitate additional investigation

Social Aggregation in Pea Aphids: Experiment and Random Walk Modeling

From bird flocks to fish schools and ungulate herds to insect swarms, social biological aggregations are found across the natural world. An ongoing challenge in the mathematical modeling of aggregations is to strengthen the connection between models and biological data by quantifying the rules that individuals follow. We model aggregation of the pea aphid, Acyrthosiphon pisum. Specifically, we conduct experiments to track the motion of aphids walking in a featureless circular arena in order to deduce individual-level rules. We observe that each aphid transitions stochastically between a moving and a stationary state. Moving aphids follow a correlated random walk. The probabilities of motion state transitions, as well as the random walk parameters, depend strongly on distance to an aphid\u27s nearest neighbor. For large nearest neighbor distances, when an aphid is essentially isolated, its motion is ballistic with aphids moving faster, turning less, and being less likely to stop. In contrast, for short nearest neighbor distances, aphids move more slowly, turn more, and are more likely to become stationary; this behavior constitutes an aggregation mechanism. From the experimental data, we estimate the state transition probabilities and correlated random walk parameters as a function of nearest neighbor distance. With the individual-level model established, we assess whether it reproduces the macroscopic patterns of movement at the group level. To do so, we consider three distributions, namely distance to nearest neighbor, angle to nearest neighbor, and percentage of population moving at any given time. For each of these three distributions, we compare our experimental data to the output of numerical simulations of our nearest neighbor model, and of a control model in which aphids do not interact socially. Our stochastic, social nearest neighbor model reproduces salient features of the experimental data that are not captured by the control

Modular Design of a Passive, Low-Cost Prosthetic Knee Mechanism to Enable Able-Bodied Kinematics for Users With Transfemoral Amputation

There is a significant need for low-cost, high-performance prosthetic knee technology for transfemoral amputees in India. Replicating able-bodied gait in amputees is biomechanically necessary to reduce the metabolic cost, and it is equally important to mitigate the socio-economic discrimination faced by amputees in developing countries due to their conspicuous gait deviations. This paper improves upon a previous study of a fully passive knee mechanism, addressing the issues identified in its user testing in India. This paper presents the design, analysis and bench-level testing of the three major functional modules of the new prosthetic knee architecture: (i) a four-bar latch mechanism for achieving stability during stance phase of walking, (ii) an early stance flexion module designed by implementing a fully adjustable mechanism, and (iii) a hydraulic rotary damping system for achieving smooth and reliable swing-phase control

Circadian signaling in Homarus americanus: Region-specific de novo assembled transcriptomes show that both the brain and eyestalk ganglia possess the molecular components of a putative clock system

Essentially all organisms exhibit recurring patterns of physiology/behavior that oscillate with a period of ~24-h and are synchronized to the solar day. Crustaceans are no exception, with robust circadian rhythms having been documented in many members of this arthropod subphylum. However, little is known about the molecular underpinnings of their circadian rhythmicity. Moreover, the location of the crustacean central clock has not been firmly established, although both the brain and eyestalk ganglia have been hypothesized as loci. The American lobster, Homarus americanus, is known to exhibit multiple circadian rhythms, and immunodetection data suggest that its central clock is located within the eyestalk ganglia rather than in the brain. Here, brain- and eyestalk ganglia-specific transcriptomes were generated and used to assess the presence/absence of transcripts encoding the commonly recognized protein components of arthropod circadian signaling systems in these two regions of the lobster central nervous system. Transcripts encoding putative homologs of the core clock proteins clock, cryptochrome 2, cycle, period and timeless were found in both the brain and eyestalk ganglia assemblies, as were transcripts encoding similar complements of putative clock-associated, clock input pathway and clock output pathway proteins. The presence and identity of transcripts encoding core clock proteins in both regions were confirmed using PCR. These findings suggest that both the brain and eyestalk ganglia possess all of the molecular components needed for the establishment of a circadian signaling system. Whether the brain and eyestalk clocks are independent of one another or represent a single timekeeping system remains to be determined. Interestingly, while most of the proteins deduced from the identified transcripts are shared by both the brain and eyestalk ganglia, assembly-specific isoforms were also identified, e.g., several period variants, suggesting the possibility of region-specific variation in clock function, especially if the brain and eyestalk clocks represent independent oscillators

The LISA Gravitational Wave Foreground: A Study of Double White Dwarfs

Double white dwarfs are expected to be a source of confusion-limited noise for the future gravitational wave observatory LISA. In a specific frequency range, this 'foreground noise' is predicted to rise above the instrumental noise and hinder the detection of other types of signals, e.g., gravitational waves arising from stellar mass objects inspiraling into massive black holes. In many previous studies only detached populations of compact object binaries have been considered in estimating the LISA gravitational wave foreground signal. Here, we investigate the influence of compact object detached and Roche-Lobe Overflow Galactic binaries on the shape and strength of the LISA signal. Since >99% of remnant binaries which have orbital periods within the LISA sensitivity range are white dwarf binaries, we consider only these binaries when calculating the LISA signal. We find that the contribution of RLOF binaries to the foreground noise is negligible at low frequencies, but becomes significant at higher frequencies, pushing the frequency at which the foreground noise drops below the instrumental noise to >6 mHz. We find that it is important to consider the population of mass transferring binaries in order to obtain an accurate assessment of the foreground noise on the LISA data stream. However, we estimate that there still exists a sizeable number (~11300) of Galactic double white dwarf binaries which will have a signal-to-noise ratio >5, and thus will be potentially resolvable with LISA. We present the LISA gravitational wave signal from the Galactic population of white dwarf binaries, show the most important formation channels contributing to the LISA disc and bulge populations and discuss the implications of these new findings.Comment: ApJ accepted. 28 pages, 11 figures (low resolution), 5 tables, some new references and changed content since last astro-ph versio

S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells

MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery

Changes in Bone Turnover Marker Levels and Clinical Outcomes in Patients With Advanced Cancer and Bone Metastases Treated With Bone Antiresorptive Agents

Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTMs) in patients with advanced cancer. We evaluated association of changes in BTMs with overall survival (OS), disease progression (DP), and disease progression in bone (DPB) in patients with advanced cancer and bone metastases following denosumab or zoledronic acid treatment. Experimental Design: This is an integrated analysis of patient-level data from three identically designed, blinded, phase III trials with patients randomized to subcutaneous denosumab or intravenous zoledronic acid. Levels of the BTMs urinary N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBSAP) measured at study entry and month 3 were analyzed. OS, DP, and DPB were compared in patients with BTMs {greater than or equal to} median vs < median based on month 3 assessments. Results: uNTx levels {greater than or equal to} the median of 10.0 nmol/mmol at month 3 were associated with significantly reduced OS compared with levels < median (HR for death 1.85, P<0.0001). sBSAP levels {greater than or equal to} median of 12.6 ng/mL were associated with significantly reduced OS compared with levels < median (HR 2.44, P<0.0001). uNTx and sBSAP levels {greater than or equal to} median at month 3 were associated with significantly greater risk of DP (HR 1.31, P<0.0001 and HR 1.71, P<0.0001, respectively) and DPB (HR 1.11, P=0.0407 and HR 1.27, P<0.0001, respectively). Conclusions: BTM levels {greater than or equal to} median after 3 months of bone antiresorptive treatment were associated with reduced OS and increased risk of DP and DPB. Assessment of uNTx and sBSAP levels after bone antiresorptive therapy may add to identification of patients at risk for worse clinical outcomes