Electron Microscopic Observations on Certain Secretory Epithelial Cells of the Gastro-Intestinal Tract in the Mouse

Abstract Not Provided

Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation

Nuclear receptors are ligand-activated transcription factors that play significant roles in various biological processes within the body, such as cell development, hormone metabolism, reproduction, and cardiac function. As transcription factors, nuclear receptors are involved in many diseases, such as diabetes, cancer, and arthritis, resulting in approximately 10-15% of the pharmaceutical drugs presently on the market being targeted toward nuclear receptors. Structurally, nuclear receptors consist of a DNA-binding domain (DBD), responsible for binding specific sequences of DNA called response elements, fused to a ligand-binding domain (LBD) through a hinge region. The LBD binds a small molecule ligand. Upon ligand binding, the LBD changes to an active conformation leading to the recruitment of coactivator (CoAC) proteins and initiation of transcription. As a result of their involvement in disease, there is an emphasis on engineering nuclear receptors for applications in gene therapy, drug discovery and metabolic engineering.Ph.D.Committee Chair: Bahareh Azizi; Committee Chair: Donald Doyle; Committee Co-Chair: Andreas Bommarius; Committee Co-Chair: Loren Williams; Committee Member: Adegboyega Oyelere; Committee Member: Nick Hud; Committee Member: Sheldon Ma

Neutrino processes in partially degenerate neutron matter

We investigate neutrino processes for conditions reached in simulations of core-collapse supernovae. Where neutrino-matter interactions play an important role, matter is partially degenerate, and we extend earlier work that addressed the degenerate regime. We derive expressions for the spin structure factor in neutron matter, which is a key quantity required for evaluating rates of neutrino processes. We show that, for essentially all conditions encountered in the post-bounce phase of core-collapse supernovae, it is a very good approximation to calculate the spin relaxation rates in the nondegenerate limit. We calculate spin relaxation rates based on chiral effective field theory interactions and find that they are typically a factor of two smaller than those obtained using the standard one-pion-exchange interaction alone.Comment: 41 pages, 9 figures, NORDITA-2011-116; added comparison figures and fit function for use in simulations, to appear in Astrophys.

Voluntary Medical Male Circumcision: A Qualitative Study Exploring the Challenges of Costing Demand Creation in Eastern and Southern Africa

BACKGROUND: This paper proposes an approach to estimating the costs of demand creation for voluntary medical male circumcision (VMMC) scale-up in 13 countries of eastern and southern Africa. It addresses two key questions: (1) what are the elements of a standardized package for demand creation? And (2) what challenges exist and must be taken into account in estimating the costs of demand creation? METHODS AND FINDINGS: We conducted a key informant study on VMMC demand creation using purposive sampling to recruit seven people who provide technical assistance to government programs and manage budgets for VMMC demand creation. Key informants provided their views on the important elements of VMMC demand creation and the most effective funding allocations across different types of communication approaches (e.g., mass media, small media, outreach/mobilization). The key finding was the wide range of views, suggesting that a standard package of core demand creation elements would not be universally applicable. This underscored the importance of tailoring demand creation strategies and estimates to specific country contexts before estimating costs. The key informant interviews, supplemented by the researchers' field experience, identified these issues to be addressed in future costing exercises: variations in the cost of VMMC demand creation activities by country and program, decisions about the quality and comprehensiveness of programming, and lack of data on critical elements needed to "trigger the decision" among eligible men. CONCLUSIONS: Based on this study's findings, we propose a seven-step methodological approach to estimate the cost of VMMC scale-up in a priority country, based on our key assumptions. However, further work is needed to better understand core components of a demand creation package and how to cost them. Notwithstanding the methodological challenges, estimating the cost of demand creation remains an essential element in deriving estimates of the total costs for VMMC scale-up in eastern and southern Africa

Mode effects between computer self-administration and telephone interviewer-administration of the PROMIS® pediatric measures, self- and proxy report

To test equivalence of scores obtained with the PROMIS® pediatric Depressive Symptoms, Fatigue, and Mobility measures across two modes of administration: computer self-administration and telephone interviewer-administration. If mode effects are found, to estimate the magnitude and direction of the mode effects

Estimating Fire Background Temperature at a Geostationary Scale-An Evaluation of Contextual Methods for AHI-8

An integral part of any remotely sensed fire detection and attribution method is an estimation of the target pixels background temperature. This temperature cannot be measured directly independent of fire radiation, so indirect methods must be used to create an estimate of this background value. The most commonly used method of background temperature estimation is through derivation from the surrounding obscuration-free pixels available in the same image, in a contextual estimation process. This method of contextual estimation performs well in cloud-free conditions and in areas with homogeneous landscape characteristics, but increasingly complex sets of rules are required when contextual coverage is not optimal. The effects of alterations to the search radius and sample size on the accuracy of contextually derived brightness temperature are heretofore unexplored. This study makes use of imagery from the AHI-8 geostationary satellite to examine contextual estimators for deriving background temperature, at a range of contextual window sizes and percentages of valid contextual information. Results show that while contextual estimation provides accurate temperatures for pixels with no contextual obscuration, significant deterioration of results occurs when even a small portion of the target pixels surroundings are obscured. To maintain the temperature estimation accuracy, the use of no less than 65% of a target pixels total contextual coverage is recommended. The study also examines the use of expanding window sizes and their effect on temperature estimation. Results show that the accuracy of temperature estimation decreases significantly when expanding the examined window, with a 50% increase in temperature variability when using a larger window size than 5×5 pixels, whilst generally providing limited gains in the total number of temperature estimates (between 0.4%4.4% of all pixels examined). The work also presents a number of case study regions taken from the AH

Terrestrial laser scanning: an operational tool for fuel hazard mapping?

Fuel hazard estimates are vital for the prediction of fire behaviour and planning fuel treatment activities. Previous literature has highlighted the potential of Terrestrial Laser Scanning (TLS) to be used to assess fuel properties. However, operational uptake of these systems has been limited due to a lack of a sampling approach that balances efficiency and data efficacy. This study aims to assess whether an operational approach utilising Terrestrial Laser Scanning (TLS) to capture fuel information over an area commensurate with current fuel hazard assessment protocols implemented in South-Eastern Australia is feasible. TLS data were captured over various plots in South-Eastern Australia, utilising both low- and high-cost TLS sensors. Results indicate that both scanners provided similar overall representation of the ground, vertical distribution of vegetation and fuel hazard estimates. The analysis of fuel information contained within individual scans clipped to 4 m showed similar results to that of the fully co-registered plot (cover estimates of near-surface vegetation were within 10%, elevated vegetation within 15%, and height estimates of near-surface and elevated strata within 0.05 cm). This study recommends that, to capture a plot in an operational environment (balancing efficiency and data completeness), a sufficient number of non-overlapping individual scans can provide reliable estimates of fuel information at the near-surface and elevated strata, without the need for co-registration in the case study environments. The use of TLS within the rigid structure provided by current fuel observation protocols provides incremental benefit to the measurement of fuel hazard. Future research should leverage the full capability of TLS data and combine it with moisture estimates to gain a full realisation of the fuel hazard

Exploring structure–activity relationships in photodynamic therapy anticancer agents based on Ir(III)-COUPY conjugates

Photodynamic therapy holds great promise as a non-invasive anticancer tool against drug-resistant cancers. However, highly effective, non-toxic, and reliable photosensitizers with operability under hypoxic conditions remain to be developed. Herein, we took the advantageous properties of COUPY fluorophores and cyclometalated Ir(III) complexes to develop novel PDT agents based on Ir(III)-COUPY conjugates with the aim of exploring structure–activity relationships. The structural modifications carried out within the coumarin scaffold had a strong impact on the photophysical properties and cellular uptake of the conjugates. All Ir(III)-COUPY conjugates exhibited high phototoxicity under green light irradiation, which was attributed to the photogeneration of ROS, while remaining non-toxic in the dark. Among them, two hit conjugates showed excellent phototherapeutic indexes in cisplatin-resistant A2780cis cancer cells, both in normoxia and in hypoxia, suggesting that photoactive therapy approaches based on the conjugation of far-red/NIR-emitting COUPY dyes and transition metal complexes could effectively tackle in vitro acquired resistance to cisplatin

Sphalerons and the Electroweak Phase Transition in Models with Higher Scalar Representations

In this work we investigate the sphaleron solution in a $SU(2)\times U(1)_X$ gauge theory, which also encompasses the Standard Model, with higher scalar representation(s) ($J^{(i)},X^{(i)}$). We show that the field profiles describing the sphaleron in higher scalar multiplet, have similar trends like the doublet case with respect to the radial distance. We compute the sphaleron energy and find that it scales linearly with the vacuum expectation value of the scalar field and its slope depends on the representation. We also investigate the effect of $U(1)$ gauge field and find that it is small for the physical value of the mixing angle, $\theta_{W}$ and resembles the case for the doublet. For higher representations, we show that the criterion for strong first order phase transition, $v_{c}/T_{c}>\eta$, is relaxed with respect to the doublet case, i.e. $\eta<1$.Comment: 20 pages, 5 figures & 1 table, published versio