Investigating evidence of high frequency glacial eustacy in the Lower Mississippian (Tournasian) Lodgepole Formation of southwest Montana : insights from conodont oxygen isotopes

This study focuses on high-frequency, subtidal-carbonate cycles (1-8 m thick) within the Woodhurst Member of the Lower Mississippian Lodgepole Formation of southwest Montana. We combined conodont-oxygen isotopes (δ18Oapatite¬) and carbonate-carbon isotopes (δ13Ccarb) with cyclostratigraphy of Woodhurst cycles to test the hypothesis that the cycles developed in response to glacial eustasy, evaluate the timing and initiation of the Late Paleozoic Ice Age (LPIA), and to better understand the carbon budget in response to cycle formation. δ18Oapatite trends across targeted cycles support the hypothesis of glacial eustatic origins along with cooling surface seawater temperatures. High-resolution δ13Ccarb analysis of whole-rock limestones within eleven cycles reveal invariant or nonsystematic δ13Ccarb trends, but the long term trend confirms a major positive excursion reported in previous studies of coeval deposits, values peak at ~ 7.5 ° in the upper S. isosticha conodont Zone

Mechanical And Computational Evaluation Of Cementitious Materials With Hollow Glass Microsphere Inclusions

The effect of volumetric replacement of cementitious materials by an inert filler known as hollow glass microspheres on elastic properties is evaluated in this study through a combined computational and experimental approach. This approach considered the variation in properties of type I Portland cement for 0, 5, 10, and 15% volume fractions of two kind of glass microspheres; one was high density with high crushing strength, and the other with a relative lower density. Using a suite of software called Virtual Cement and Concrete Testing Laboratory (VCCTL), the microstructural details were determined for 80% degree of hydration of the cement mixture for these different volume fractions. The VCCTL-generated three dimensional heterogeneous microstructures with various micro-constituents, such as the C-S-H gel, tricalcium silicate, and other cement byproducts, were explicitly modeled in ABAQUS© commercial finite element code. The representative volume element (RVE) in ABAQUS was a 100x100x100 μm3 cube. Since the symmetry as well as the anisotropy of the cementitious material system is not fully established, iso-strain based boundary conditions were applied to this RVE towards determining various elements of the elastic tensor. The computationally calculated elastic moduli compared reasonably well with data from quasi-static compression tests for various volume fractions of the glass microspheres

Microcomputed Tomography Applications in Bone and Mineral Research

Microcomputed tomography (μCT) has evolved as a development of simple X-ray imaging into an indispensable technique used in both laboratory research and clinical diagnostics. Commercially available systems are capable of creating images at sub-micrometer resolutions to map out the complex web of trabecular bone in small animals, and offer an accurate measurement of bone mineral density for patients at risk of osteoporotic fractures. This review describes the development of μCT, its ability to analyze bone, and how it can be used alongside other clinical and laboratory techniques. μCT offers a non-destructive alternative for imaging mineralized tissues with no required preparation and can also be utilized with living specimen to track skeletal development

VUV Optical Properties of Rare Earth Doped YPO4 Prepared by Different Routes

The optical properties of nanocrystalline YPO4:Ln3+ (Ln = Eu, Sm, Tb) prepared via co-precipitation are compared to larger crystallites of YPO4:Ln3+ prepared via traditional solid state reaction. In larger crystals (~330 nm) a distinct peak is observed at 150 nm in the excitation spectra, the intensity of which decreases markedly in smaller crystals (~20 nm). Using excitation and reflectance spectroscopy, host–to–activator energy transfer efficiencies were calculated for Y1-xPO4:Lnx3+ (0.01 ≤ x ≤ 0.10). From the transfer efficiency data, we estimate that trapping by Eu3+ and Sm3+ is at least five times more efficient than trapping by Tb3+ for excitation at the band edge. The fraction of energy lost to the surface or grain boundaries for excitation at 150 nm and 138 nm is also estimated. We propose that in the samples prepared via co-precipitation, an amorphous phase forms at grain boundaries that is responsible for the loss of efficiency under 150 nm excitation

Effects of oil and natural gas development on territory occupancy of ferruginous hawks and golden eagles in Wyoming, USA

Energy development is expanding rapidly across the western US. Negative effects have been documented for some wildlife, but consequences of development are unclear for other taxa, including raptors. We had the opportunity to examine effects of oil and natural gas development on two raptor species of conservation concern, ferruginous hawks (Buteo regalis) and golden eagles (Aquila chrysaetos), in sagebrush steppe and prairie habitats of Wyoming. We surveyed nest sites of these species using fixed-wing aircraft during 2010–2011, and monitored occupancy of the resulting sample of historically active breeding territories during 2011–2013 for ferruginous hawks, and 2012–2013 for golden eagles. We used single-season occupancy models to evaluate post-construction effects of oil and natural gas development in the context of other factors predicted to influence use of territories by these species, including prey abundance, nest site characteristics, and vegetation. An additional objective was to demonstrate a monitoring protocol for raptors in Wyoming that used probabilistic sampling and accounted for imperfect detection. In support of our predictions, probability of territory occupancy by ferruginous hawks had a strong positive relationship to abundance of ground squirrels (Urocitellus spp.), a strong negative relationship to vegetative cover of sagebrush (Artemisia spp.), and was slightly higher for artificial nest platforms compared to other substrates; and territory occupancy for golden eagles had a strong positive relationship to nest height. Contrary to our predictions, density of oil and natural gas infrastructure was not strongly related to occupancy for either species, and prey abundance was not related to occupancy for golden eagles. The only anthropogenic factor that influenced occupancy for either species was density of improved roads not associated with oil and natural gas fields, which had a weak positive correlation with occupancy for ferruginous hawks, contrary to our predictions. Annual occupancy probability did not vary significantly for either species during our study, but environmental factors associated with occupancy and the strength of relationships varied among years for both species, suggesting occupancy was influenced by additional factors not included in our analysis (e.g. weather, regional dynamics). Detection probability for both species was <1, and strongly influenced by nest substrates. For ferruginous hawks, detection probability varied significantly between years, and was positively associated with nest height. For golden eagles, detection probability was significantly higher in territories with nests on trees, shrubs, and anthropogenic structures, compared to those on cliffs and rock outcrops, with a weak negative trend in detection rates across survey occasions during one year. Our results suggest ferruginous hawks and golden eagles used breeding territories that contained active oil and gas roads and well pads, and density of infrastructure in these territories did not affect their probability of use. However, we advise that limitations of our approach (i.e. post-construction, short-term, observational study) make our results most relevant as a baseline for ongoing monitoring of these species. We suggest protection efforts should be focused on ferruginous hawk territories with abundant ground squirrels and low natural cover of sagebrush, and golden eagle territories with higher nest sites. We recommend conserving populations and habitats of burrowing mammals, mitigating loss of nests using artificial platforms, and long-term monitoring of ferruginous hawks and golden eagles using robust methods that account for imperfect detection

Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a genetic disease of Type I collagen and collagen-associated pathways that results in brittle bone behavior characterized by fracture and reduced mechanical properties. Based on previous work in our laboratory showing that raloxifene (RAL) can significantly improve bone mechanical properties through non-cellular mechanisms, we hypothesized that raloxifene would improve the mechanical properties of OI bone. In experiment 1, tibiae from female wild type (WT) and homozygous oim mice were subjected to in vitro soaking in RAL followed by mechanical tests. RAL soaking resulted in significantly higher post-yield displacement (+75% in WT, +472% in oim; p<0.004), with no effect on ultimate load or stiffness, in both WT and oim animals. In experiment 2, eight-week old WT and oim male mice were treated for eight weeks with saline vehicle (VEH) or RAL. Endpoint measures included assessment of in vivo skeletal fractures, bone density/geometry and mechanical properties. In vivo skeletal fractures of the femora, assessed by micro CT imaging, were significantly lower in oim-RAL (20%) compared to oim-VEH (48%, p=0.047). RAL led to significantly higher DXA-based BMD (p<0.01) and CT-based trabecular BV/TV in both WT and oim animals compared to those treated with VEH. Fracture toughness of the femora was lower in oim mice compared to WT and improved with RAL in both genotypes. These results suggest that raloxifene reduces the incidence of fracture in this mouse model of oim. Furthermore, they suggest that raloxifene's effects may be the result of both cellular (increased bone mass) and non-cellular (presumably changes in hydration) mechanisms, raising the possibility of using raloxifene, or related compounds, as a new approach for treating bone fragility associated with OI.S10 RR023710/RR/NCRR NIH HHS/United State

Peri- and Postnatal Effects of Prenatal Adenoviral VEGF Gene Therapy in Growth-Restricted Sheep

Uterine artery (UtA) adenovirus vector (Ad)-mediated over-expression of vascular endothelial growth factor (VEGF) enhances uterine blood flow in normal sheep pregnancy and increases fetal growth in the overnourished adolescent sheep model of fetal growth restriction (FGR). Herein we examined its impact on gestation length, neonatal survival, early postnatal growth and metabolism. Singleton-bearing ewes were evenly allocated to receive Ad.VEGF-A165(5 x 10(10)particles/ml, 10 ml, n =17) or Saline (10 ml, n = 16) injected into each UtA at laparotomy (0.6 gestation). Fetal growth was serially monitored (blind) by ultrasound until delivery. Lambs were weighed and blood-sampled weekly and a glucose tolerance test performed (68d postnatal age). Hepatic DNA/RNA was extracted at necropsy (83d postnatal age) to examine methylation status of eight somatotropic axis genes. ITALIC! IGF1mRNA and protein expression were measured by RT-PCR and radioimmunoassay, respectively. All pregnancies remained viable following Ad.VEGF-A165treatment. Fetal abdominal circumference and renal volume were greater in Ad.VEGF-A165versus Saline groups at 21/28 days (p ≤ 0.04) post-injection. At delivery, gestation length (p = 0.07), lamb birthweight (p = 0.08), umbilical girth (p = 0.06) and plasma glucose (p=0.09) tended to be greater in Ad.VEGF-A165treated lambs. Levels of neonatal intervention required to ensure survival was equivalent between groups. Absolute postnatal growth rate (p = 0.02), insulin area-under-the-curve (p = 0.04) and carcass weight at necropsy (p = 0.04) were increased by Ad.VEGF-A165treatment. There was no impact on markers of insulin sensitivity or methylation/expression of key genes involved in somatic growth. Ad.VEGF-A165gene therapy increased fetal growth in a sheep FGR model and lambs continued to thrive during the neonatal and early postnatal period

Evaluating the Bioavailability of Carbamazepine Using a Novel SNEDDS Formulation

Central to the mechanism of how drugs work are the concepts of solubility and bioavailability. Drugs enter the body via absorption into the bloodstream, arrive at the target location, and bind to receptors to cause an effect. Drugs need to be soluble enough to pass through the cell membrane to enter and exit the bloodstream. Higher solubility generally correlates to higher bioavailability. Additionally, the smaller the particle size, the easier the drug will pass through the membrane into the blood plasma. Researchers have designed a system to categorize solubility class: Class I being high permeability and high solubility, Class II high permeability and low solubility, Class III low permeability and high solubility, and Class IV low permeability and low solubility. The study will use a Class II anticonvulsant, carbamazepine (CBZ). CBZ is a suitable candidate for this study because it requires a higher bioavailability due to its need to cross the blood brain barrier and act on the trigeminal nucleus. To increase bioavailability researchers have tried crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification. These methods have been successful at increasing bioavailability, but this experiment will focus on reducing particle size into a new self-emulsifying formulation. In particular, the formulation of CBZ in this study is a self nano-emulsifying drug delivery system (SNEDDS), which shows more promise than previous methods to increase bioavailability. This study will create a SNEDDS formulation as a nasal nebulizer mist delivery and compare it to a FDA approved oral suspension using a crossover rat model design. Sixteen Sprague-Dawley rats will be ordered through Central State University and normalized to the study environment for a minimum of one week. Pending IACUC approval from Central State University, the tail vein method will be used to collect blood samples. The samples will be stored until needed for analysis using ELISA, enzyme-linked immunosorbent assay, which will be used to determine the concentration of CBZ in blood plasma

Evaluating the Bioavailability of Carbamazepine Using a Novel SNEDDS Formulation

Carbamazepine (CBZ) is an anticonvulsant drug primarily used to treat epilepsy, bipolar disorder, trigeminal and glossopharyngeal neuralgia. CBZ is a lipophilic, poorly soluble drug that belongs to the class-2 category according to the Biopharmaceutics Classification System. As a class-2 drug, the plasma concentration of CBZ is limited by its ability to diffuse across biological membranes. To increase its bioavailability, different methods such as crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification were explored. Of these methods, Self Nano Emulsifying Drug Delivery Systems (SNEDDS) have shown to reduce particle size of CBZ molecules and improve its solubility. However, the bioavailability of CBZ administered as SNEDDS are not yet investigated. Given this background, the current study proposes to evaluate the bioavailability of these novel drug delivery systems using a rat model. The study is designed as a randomized controlled crossover experiment using 10-12 Sprague-Dawley rats divided equally into two groups. For this study, blood samples will be collected at 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes after administering two different formulations of CBZ nanoemulsions and stored at -20°C until ready for analysis. Plasma concentrations of CBZ will be determined by HPLC method. An unpaired t-test will be used to compare the significance between the two sets of data