The role of sexual dimorphism in cartilage tissue regeneration

Osteoarthritis is a degenerative joint disease characterized by progressive erosion of the articular cartilage. Epidemiological studies have established a relationship between osteoarthritis and menopause suggesting that estrogen may be important in the development of cartilage regeneration therapies. The overall goal of this research project was to advance the field of cartilage tissue regeneration by investigating the role of 17 ß -estradiol (E2), an active estrogen metabolite, on the chondrocyte phenotype. The central hypothesis was that E2 plays an important and sex-specific role in regulating chondrogenesis. Specific Aim-1 focused on establishing and characterizing a primary human articular chondrocyte (HAC) cell source, and then examining the response of the cells in culture to E2. It was demonstrated that the response of HACs to E2 treatment was sex-specific despite both male and females cells expressing estrogen receptors. Female HACs showed changes in proliferation, matrix production, and differentiation while male cells did not. In addition, the female response was regulated through a rapid membrane signaling pathway mediated by protein kinase C. Specific Aim-2 involved establishing an ovariectomized animal model to investigate the effects of E2 on orthopaedic tissue implants. Human demineralized bone matrix (DBM) was implanted intramuscularly into female nude mice and rats. Ovariectomy was shown to reduce the ability of DBM to induce the formation of cartilage and bone tissue. Moreover, the inductive properties of DBM were reestablished with subcutaneous E2 supplementation. Specific Aim-3 entailed developing and characterizing a microencapsulation method for in vitro culture and in vivo delivery of chondrocytes to study the effects of E2 on chondrogenesis. Rat growth plate chondrocytes and HACs were microencapsulated in alginate using an extrusion method in conjunction with high electrostatic potential. Chondrocytes maintained their phenotype in alginate suspension but were unable to form cartilage tissue when implanted into our animal model. Further optimization of the system is required before the role of E2 on chondrogenesis of tissue engineered constructs can be determined. In summary, our results suggest that the successful production of tissue engineered therapies will likely depend on understanding and manipulating the actions of sex hormones in both the in vitro and in vivo environment.Ph.D.Committee Chair: Boyan, Barbara; Committee Member: Bonassar, Lawrence; Committee Member: Sambanis, Anthanassios; Committee Member: Schwartz, Zvi; Committee Member: Wick, Timoth

The end of the television licence fee? Applying the German household levy model to the United Kingdom

While the United Kingdom (UK) government has renewed the BBC Royal Charter until 2027 and confirmed that the television licence fee will last for this period, a medium-term shift from the television licence fee to a household levy is still a policy option. Drawing on the German experience, we discuss the probable difficulties, possible benefits and the overall implications of such a shift in the UK. The article employs a comparative media policy analysis. After a brief history of public service broadcasting funding in the UK, we provide an outline of the recent German public service media funding reform. We point out the difficulties from the German model to predict the future total revenues and elaborate on the suitability of it in the UK context, contrasting the possibilities of policy transfer and policy failure. </jats:p

Model-theoretic properties of nilpotent groups and Lie algebras

We give a systematic study of the model theory of generic nilpotent groups and Lie algebras. We show that the Fra\"iss\'e limit of 2-nilpotent groups of exponent $p$ studied by Baudisch is 2-dependent and NSOP$_{1}$. We prove that the class of $c$-nilpotent Lie algebras over an arbitrary field, in a language with predicates for a Lazard series, is closed under free amalgamation. We show that for $2 < c$, the generic $c$-nilpotent Lie algebra over $\mathbb{F}_{p}$ is strictly NSOP$_{4}$ and $c$-dependent. Via the Lazard correspondence, we obtain the same result for $c$-nilpotent groups of exponent $p$, for an odd prime $p > c$

Effects of X-irradiation on Potassium Flux in Isolated Nerves

The purpose of this study, therefore, was threefold in nature: (1) to determine the effects of x-irradiation on the influx and efflux of potassium in compound nerve fibers (2) to attempt to relate the radiation-induced changes in electrical activity with potassium flux and (3) to use the information obtained to gain insight into the possible cellular site (s) of radiation insult to compound nerves

Deep Search For Molecular Oxygen in TW Hya

The dominant form of oxygen in cold molecular clouds is gas-phase carbon monoxide (CO) and ice-phase water (H$_2$O). Yet, in planet-forming disks around young stars, gas-phase CO and H$_2$O are less abundant relative to their ISM values, and no other major oxygen-carrying molecules have been detected. Some astrochemical models predict that gas-phase molecular oxygen (O$_2$) should be a major carrier of volatile oxygen in disks. We report a deep search for emission from the isotopologue $^{16}$O$^{18}$O ($N_J=2_1-0_1$ line at 233.946 GHz) in the nearby protoplanetary disk around TW Hya. We used imaging techniques and matched filtering to search for weak emission but do not detect $^{16}$O$^{18}$O. Based on our results, we calculate upper limits on the gas-phase O$_2$ abundance in TW Hya of $(6.4-70)\times10^{-7}$ relative to H, which is $2-3$ orders of magnitude below solar oxygen abundance. We conclude that gas-phase O$_2$ is not a major oxygen-carrier in TW Hya. Two other potential oxygen-carrying molecules, SO and SO$_2$, were covered in our observations, which we also do not detect. Additionally, we report a serendipitous detection of the C$^{15}$N $N_J = 2_{5/2}-1_{3/2}$ hyperfine transitions, $F = 3 - 2$ and $F = 2 - 1$, at 219.9 GHz, which we found via matched filtering and confirm through imaging.Comment: 10 pages, 6 figures, Accepted for publication in Ap

Insecticide Resistance Mechanisms in the Green Peach Aphid Myzus persicae (Hemiptera: Aphididae) I: A Transcriptomic Survey

BACKGROUND: Insecticide resistance is one of the best examples of rapid micro-evolution found in nature. Since the development of the first synthetic insecticide in 1939, humans have invested considerable effort to stay ahead of resistance phenotypes that repeatedly develop in insects. Aphids are a group of insects that have become global pests in agriculture and frequently exhibit insecticide resistance. The green peach aphid, Myzus persicae, has developed resistance to at least seventy different synthetic compounds, and different insecticide resistance mechanisms have been reported worldwide. METHODOLOGY/PRINCIPAL FINDINGS: To further characterize this resistance, we analyzed genome-wide transcriptional responses in three genotypes of M. persicae, each exhibiting different resistance mechanisms, in response to an anti-cholinesterase insecticide. The sensitive genotype (exhibiting no resistance mechanism) responded to the insecticide by up-regulating 183 genes primarily ones related to energy metabolism, detoxifying enzymes, proteins of extracellular transport, peptidases and cuticular proteins. The second genotype (resistant through a kdr sodium channel mutation), up-regulated 17 genes coding for detoxifying enzymes, peptidase and cuticular proteins. Finally, a multiply resistant genotype (carrying kdr and a modified acetylcholinesterase), up-regulated only 7 genes, appears not to require induced insecticide detoxification, and instead down-regulated many genes. CONCLUSIONS/SIGNIFICANCE: This study suggests strongly that insecticide resistance in M. persicae is more complex that has been described, with the participation of a broad array of resistance mechanisms. The sensitive genotype exhibited the highest transcriptional plasticity, accounting for the wide range of potential adaptations to insecticides that this species can evolve. In contrast, the multiply resistant genotype exhibited a low transcriptional plasticity, even for the expression of genes encoding enzymes involved in insecticide detoxification. Our results emphasize the value of microarray studies to search for regulated genes in insects, but also highlights the many ways those different genotypes can assemble resistant phenotypes depending on the environmental pressure

A comprehensive radial velocity error budget for next generation Doppler spectrometers

We describe a detailed radial velocity error budget for the NASA-NSF Extreme Precision Doppler Spectrometer instrument concept NEID (NN-explore Exoplanet Investigations with Doppler spectroscopy). Such an instrument performance budget is a necessity for both identifying the variety of noise sources currently limiting Doppler measurements, and estimating the achievable performance of next generation exoplanet hunting Doppler spectrometers. For these instruments, no single source of instrumental error is expected to set the overall measurement floor. Rather, the overall instrumental measurement precision is set by the contribution of many individual error sources. We use a combination of numerical simulations, educated estimates based on published materials, extrapolations of physical models, results from laboratory measurements of spectroscopic subsystems, and informed upper limits for a variety of error sources to identify likely sources of systematic error and construct our global instrument performance error budget. While natively focused on the performance of the NEID instrument, this modular performance budget is immediately adaptable to a number of current and future instruments. Such an approach is an important step in charting a path towards improving Doppler measurement precisions to the levels necessary for discovering Earth-like planets.Comment: 20 pages, 12 figures, published in Proc. of SPIE Astronomical Telescopes + Instrumentation 201