Origin of Jurassic Carbonate Nodules in Southeastern Wyoming

The Morrison Formation of the Western United States is famous for the dinosaurs and other fossils that have been excavated from its beds. It was deposited during the Late Jurassic in a semi-arid, savannah-like environment. The Morrison Formation is remarkably extensive, with outcrops across eight states; however attempts to correlate between Wyoming and the Colorado Plateau have proven difficult. The goal of this research is to determine the origin of carbonate rocks from the Morrison Formation beds exposed on the Spring Creek Preserve in southeastern Wyoming, and to assess their potential for lithostratigphic correlations. A wide range of research techniques were employed, ranging from macroscopic observations in the field to geochemical and isotopic analyses. Field relationships and macro- and microtextures of nodular and calcareous units are consistent with carbonate mineral deposition of freshwater lacustrine muds and the development of palustrine limestones, nodules and calcrete as the micritic muds were exposed and desiccated. Strontium isotope data suggest that the nodules developed from alteration of nearby lacustrine carbonates with little exogenous input. The thickness and level of development of the nodular carbonate units below the mid-Morrison unconformity at 42 m and observed in nearby localities suggests an extended period of subaerial exposure and desiccation in the study area during middle Morrison time. If the presence of these palustrine carbonates found throughout Wyoming is the result of a synchronous regional lake-level lowstand, it is plausible that this nodular horizon correlates to the Mid-Morrison paleosol unconformity identified Utah and Colorado. The strontium isotope composition of a belemnite from the underlying Sundance Formation corresponds to a Late Jurassic Oxfordian age (161-157 million years ago) for this unit and places a maximum age for the Morrison Formation in the Spring Creek Reserve study area

Probing Binding Interactions of Cytisine Derivatives to the α4β2 Nicotinic Acetylcholine Receptor

Nicotinic acetylcholine receptors (nAChRs) are crucial for communication between synapses in the central nervous system. As such, they are also implicated in several neuropsychiatric and addictive diseases. Cytisine is a partial agonist of some nAChRs and has been used for smoking cessation. Previous studies have established a binding model for several agonists to several nAChR subtypes. Here, we evaluate the extent to which this model applies to cytisine at the α4β2 nAChR, which is a subtype that is known to play a prominent role in nicotine addiction. Along with the commonly seen cation−π interaction and two hydrogen bonds, we find that cytisine makes a second cation−π interaction at the agonist binding site. We also evaluated a series of C(10)-substituted cytisine derivatives, using two-electrode voltage-clamp electrophysiology and noncanonical amino acid mutagenesis. Double-mutant cycle analyses revealed that C(10) substitution generally strengthens the newly established second cation−π interaction, while it weakens the hydrogen bond typically seen to LeuE in the complementary subunit. The results suggest a model for how cytisine derivatives substituted at C(10) (as well as C(9)/C(10)) adjust their binding orientation, in response to pyridone ring substitution

Multidisciplinary Management of Breast Cancer During Pregnancy

Although breast cancer during pregnancy (BCDP) is rare (occurring with only 0.4% of all BC diagnoses in female patients aged 16–49 years), management decisions are challenging to both the patient and the multidisciplinary team

A Chandra observation of the ultraluminous infrared galaxy IRAS 19254--7245 (the Superantennae): X-ray emission from the Compton-thick AGN and the diffuse starburst

We present a {\it Chandra} observation of IRAS 19254--7245, a nearby ULIRG also known as {\it the Superantennae}. The high spatial resolution of {\it Chandra} allows us to disentangle for the first time the diffuse starburst emission from the embedded Compton-thick AGN. The 2-10 keV spectrum of the AGN emission is fitted by a flat power-law $\Gamma=1.3$) and a He-like Fe K$\alpha$ line with EW$\sim$1.5 keV, consistent with previous observations. The Fe K$\alpha$ line profile could be resolved as a blend of a neutral 6.4 keV line and an ionized 6.7 keV (He-like) or 6.9 keV (H-like) line. Variability is detected compared with the previous {\it XMM-Newton} and {\it suzaku} observations, demonstrating the compact size of the iron line emission. We fit the spectrum of the galaxy-scale extended emission excluding the AGN and other bright point sources with a soft thermal component with kT~0.8 keV. The luminosity of the extended emission is about one order of magnitude lower than that of the AGN. The basic physical and structural properties of the extended emission are fully consistent with a galactic wind being driven by the starburst (no contribution to the feedback by the AGN is required). A candidate ultra-luminous X-ray source is detected 8\arcsec\ south of the southern nucleus. The 0.3-10 keV luminosity of this off-nuclear point source is ~$6\times 10^{40}$ erg s$^{-1}$ if the emission is isotropic and the source is associated with the Superantennae.Comment: 31 pages, 10 figures, submitted to Ap

Automated Coronal Hole Detection using Local Intensity Thresholding Techniques

We identify coronal holes using a histogram-based intensity thresholding technique and compare their properties to fast solar wind streams at three different points in the heliosphere. The thresholding technique was tested on EUV and X-ray images obtained using instruments onboard STEREO, SOHO and Hinode. The full-disk images were transformed into Lambert equal-area projection maps and partitioned into a series of overlapping sub-images from which local histograms were extracted. The histograms were used to determine the threshold for the low intensity regions, which were then classified as coronal holes or filaments using magnetograms from the SOHO/MDI. For all three instruments, the local thresholding algorithm was found to successfully determine coronal hole boundaries in a consistent manner. Coronal hole properties extracted using the segmentation algorithm were then compared with in situ measurements of the solar wind at 1 AU from ACE and STEREO. Our results indicate that flux tubes rooted in coronal holes expand super-radially within 1 AU and that larger (smaller) coronal holes result in longer (shorter) duration high-speed solar wind streams

Perturbation theory for cosmologies with nonlinear structure

The next generation of cosmological surveys will operate over unprecedented scales, and will therefore provide exciting new opportunities for testing general relativity. The standard method for modelling the structures that these surveys will observe is to use cosmological perturbation theory for linear structures on horizon-sized scales, and Newtonian gravity for non-linear structures on much smaller scales. We propose a two-parameter formalism that generalizes this approach, thereby allowing interactions between large and small scales to be studied in a self-consistent and well-defined way. This uses both post-Newtonian gravity and cosmological perturbation theory, and can be used to model realistic cosmological scenarios including matter, radiation and a cosmological constant. We find that the resulting field equations can be written as a hierarchical set of perturbation equations. At leading-order, these equations allow us to recover a standard set of Friedmann equations, as well as a Newton-Poisson equation for the inhomogeneous part of the Newtonian energy density in an expanding background. For the perturbations in the large-scale cosmology, however, we find that the field equations are sourced by both non-linear and mode-mixing terms, due to the existence of small-scale structures. These extra terms should be expected to give rise to new gravitational effects, through the mixing of gravitational modes on small and large scales - effects that are beyond the scope of standard linear cosmological perturbation theory. We expect our formalism to be useful for accurately modelling gravitational physics in universes that contain non-linear structures, and for investigating the effects of non-linear gravity in the era of ultra-large-scale surveys.Comment: "21 pages, 2 appendices. Equations (29) and (80) have been corrected from the published version.

Probing Binding Interactions of Cytisine Derivatives to the α4β2 Nicotinic Acetylcholine Receptor

Nicotinic acetylcholine receptors (nAChRs) are crucial for communication between synapses in the central nervous system. As such, they are also implicated in several neuropsychiatric and addictive diseases. Cytisine is a partial agonist of some nAChRs and has been used for smoking cessation. Previous studies have established a binding model for several agonists to several nAChR subtypes. Here, we evaluate the extent to which this model applies to cytisine at the α4β2 nAChR, which is a subtype that is known to play a prominent role in nicotine addiction. Along with the commonly seen cation−π interaction and two hydrogen bonds, we find that cytisine makes a second cation−π interaction at the agonist binding site. We also evaluated a series of C(10)-substituted cytisine derivatives, using two-electrode voltage-clamp electrophysiology and noncanonical amino acid mutagenesis. Double-mutant cycle analyses revealed that C(10) substitution generally strengthens the newly established second cation−π interaction, while it weakens the hydrogen bond typically seen to LeuE in the complementary subunit. The results suggest a model for how cytisine derivatives substituted at C(10) (as well as C(9)/C(10)) adjust their binding orientation, in response to pyridone ring substitution

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Background Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation. Methods We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died. Results Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005). Conclusions Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes

Measuring the Physiologic Properties of Oral Lesions Receiving Fractionated Photodynamic Therapy

Photodynamic therapy (PDT) can treat superficial, early‐stage disease with minimal damage to underlying tissues and without cumulative dose‐limiting toxicity. Treatment efficacy is affected by disease physiologic properties, but these properties are not routinely measured. We assessed diffuse reflectance spectroscopy (DRS) for the noninvasive, contact measurement of tissue hemoglobin oxygen saturation (StO2) and total hemoglobin concentration ([tHb]) in the premalignant or superficial microinvasive oral lesions of patients treated with 5‐aminolevulinic acid (ALA)‐PDT. Patients were enrolled on a Phase 1 study of ALA‐PDT that evaluated fluences of 50, 100, 150 or 200 J cm−2 delivered at 100 mW cm−2. To test the feasibility of incorporating DRS measurements within the illumination period, studies were performed in patients who received fractionated (two‐part) illumination that included a dark interval of 90–180 s. Using DRS, tissue oxygenation at different depths within the lesion could also be assessed. DRS could be performed concurrently with contact measurements of photosensitizer levels by fluorescence spectroscopy, but a separate noncontact fluorescence spectroscopy system provided continuous assessment of photobleaching during illumination to greater tissue depths. Results establish that the integration of DRS into PDT of early‐stage oral disease is feasible, and motivates further studies to evaluate its predictive and dosimetric value.Diffuse reflectance spectroscopy with a contact probe was employed as part of a fluorescence and reflectance spectroscopy system to measure the tissue hemoglobin oxygen saturation and hemoglobin content of lesions of premalignant or early microinvasive cancer of the oral cavity. Studies demonstrate the feasibility of incorporating these measurements into treatment with fractionated (two‐part) photodynamic therapy (PDT) using 5‐aminolevulinic acid. Patient‐specific differences in physiologic parameters were detectable at baseline and at times during and after PDT. Photobleaching of photosensitizer was measured by its fluorescence. Results establish the utility of rationally designed spectroscopy probes toward personalized dosimetry in PDT of oral disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113767/1/php12475.pd