Modeling of gas generation from the Cameo coal zone in the Piceance Basin, Colorado

The gas generative potential of the Cretaceous Cameo coal in the Piceance Basin, northwestern Colorado, was evaluated quantitatively by sealed gold tube pyrolysis. The H/C and O/C elemental ratios show that pyrolyzed Cameo coal samples follow the Van Krevelen humic coal evolution pathway, reasonably simulating natural coal maturation. Kinetic parameters (activation energy and frequency factor) for gas generation and vitrinite reflectance (Ro) changes were calculated from pyrolysis data. Experimental Ro results from this study are not adequately predicted by published Ro kinetics and indicate the necessity of deriving basin-specific kinetic parameters when building predictive basin models. Using derived kinetics for Ro evolution and gas generation, basin modeling was completed for 57 wells across the Piceance Basin, which enabled the mapping of coal-rank and coalbed gas potential. Quantities of methane generated at approximately 1.2% Ro are about 300 standard cubic feet per ton (scf/ton) and more than 2500 scf/ton (in-situ dry-ash-free coal) at Ro values reaching 1.9%. Gases generated in both low- and high-maturity coals are less wet, whereas the wetter gas is expected where Ro is approximately 1.4–1.5%. As controlled by regional coal rank and net coal thickness, the largest in-place coalbed gas resources are located in the central part of the basin, where predicted volumes exceed 150 bcf/mi^2, excluding gases in tight sands

The Turbulent Warm Ionized Medium: Emission Measure Distribution and MHD Simulations

We present an analysis of the distribution of H-alpha emission measures for the warm ionized medium (WIM) of the Galaxy using data from the Wisconsin H-Alpha Mapper (WHAM) Northern Sky Survey. Our sample is restricted to Galactic latitudes |b| > 10. We removed sightlines intersecting nineteen high-latititude classical H II regions, leaving only sightlines that sample the diffuse WIM. The distribution of EM sin |b| for the full sample is poorly characterized by a single normal distribution, but is extraordinarily well fit by a lognormal distribution, with = 0.146 +/- 0.001 and standard deviation 0.190 +/- 0.001. drops from 0.260 +/- 0.002 at Galactic latitude 10<|b|<30 to 0.038 +/- 0.002 at Galactic latitude 60<|b|<90. The distribution may widen slightly at low Galactic latitude. We compare the observed EM distribution function to the predictions of three-dimensional magnetohydrodynamic simulations of isothermal turbulence within a non-stratified interstellar medium. We find that the distribution of EM sin |b| is well described by models of mildy supersonic turbulence with a sonic Mach number of ~1.4-2.4. The distribution is weakly sensitive to the magnetic field strength. The model also successfully predicts the distribution of dispersion measures of pulsars and H-alpha line profiles. In the best fitting model, the turbulent WIM occupies a vertical path length of 400-500 pc within the 1.0-1.8 kpc scale height of the layer. The WIM gas has a lognormal distribution of densities with a most probable electron density n_{pk} = 0.03 cm^{-3}. We also discuss the implications of these results for interpreting the filling factor, the power requirement, and the magnetic field of the WIM.Comment: 16 pages, 13 figures, ApJ in press. Replacement reflects version accepted for publicatio

Guidelines for the Management of Severe Head Injury: Are Emergency Physicians Following Them?

The Brain Trauma Foundation published “Guidelines for the Management of Severe Head Injury” in 1995. These evidence-based clinical guidelines (CGs) recommended against prophylactic hyperventilation and glucocorticoid use and advocated for aggressive blood pressure (BP) resuscitation, and the careful use of mannitol. Objective: To survey Michigan emergency physicians (MEPs) to test their adherence to these guidelines. Methods: An anonymous mail survey was sent to all 566 MEPs who are members of the American College of Emergency Physicians. Three clinical scenarios involving severe head injury were presented, all with Glasgow Coma Scale (GCS) scores of 8 or less. The physicians were asked to choose from 15 diagnostic and treatment options, which included: intubation and hyperventilation, BP resuscitation, intravenous (IV) mannitol administration, and IV glucocorticoid administration. Results: Three hundred nineteen (56%) surveys were returned. Forty-six percent [95% confidence interval (95% CI) = 40% to 51%] of the MEPs elected to use prophylactic hyperventilation; very few administered IV glucocorticoids. Seventy-eight percent (95% CI = 75% to 81%) corrected hypotension with systolic BP < 90 mm Hg; 83% (95% CI = 80% to 86%) also administered mannitol appropriately. Conclusions: A majority of MEPs are managing severe head injury patients in accordance with the “Guidelines for the Management of Severe Head Injury,” with the exception of avoiding prophylactic hyperventilation. More education and/or exposure to the evidence regarding prophylactic hyperventilation of severely head injured patients may improve adherence to the guidelines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74731/1/aemj.9.8.806.pd

Developmental appearance of factors that bind specifically to cis-regulatory sequences of a gene expressed in the sea urchin embryo

Previous gene-transfer experiments have identified a 2500-nucleotide 5' domain of the CyIIIa cytoskeletal actin gene, which contains cis-regulatory sequences that are necessary and sufficient for spatial and temporal control of CyIIIa gene expression during embryogenesis. This gene is activated in late cleavage, exclusively in aboral ectoderm cell lineages. In this study, we focus on interactions demonstrated in vitro between sequences of the regulatory domain and proteins present in crude extracts derived from sea urchin embryo nuclei and from unfertilized eggs. Quantitative gel-shift measurements are utilized to estimate minimum numbers of factor molecules per embryo at 24 hr postfertilization, when the CyIIIa gene is active, at 7 hr, when it is still silent, and in the unfertilized egg. We also estimate the binding affinity preferences (K_r) of the various factors for their respective sites, relative to their affinity for synthetic DNA competitors. At least 14 different specific interactions occur within the regulatory regions, some of which produce multiple DNA-protein complexes. Values of K_r range from approximately 2 x 10^4 to approximately 2 x 10^6 for these factors under the conditions applied. With one exception, the minimum factor prevalences that we measured in the 400-cell 24-hr embryo nuclear extracts fell within the range of 2 x 10^5 to 2 x 10^6 molecules per embryo, i.e., a few hundred to a few thousand molecules per nucleus. Three developmental patterns were observed with respect to factor prevalence: Factors reacting at one site were found in unfertilized egg cytoplasm at about the same level per egg or embryo as in 24-hr embryo nuclei; factors reacting with five other regions of the regulatory domain are not detectable in egg cytoplasm but in 7-hr mid-cleavage-stage embryo, nuclei are already at or close to their concentrations in the 24-hr embryo nuclei; and factors reacting with five additional regions are not detectable in egg cytoplasm and are low in 7-hr embryo nuclei, i.e., ⩽10% per embryo of the level they attain in 24-hr embryo nuclei. The rise in concentration of factors of the latter class could provide the proximal cause for the temporal activation of the CyIIIa gene at the early blastula stage

Effects of Phosphodiesterase 3A Modulation on Murine Cerebral Microhemorrhages

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development. Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and cerebral amyloid angiopathy (CAA)-associated mouse models of CMH. The PDE3A pathway was modulated using two approaches: genetic deletion of PDE3A and pharmacological inhibition of PDE3A by cilostazol. The effects of PDE3A pathway modulation on H&E- and Prussian blue (PB)-positive CMH development, BBB function (IgG, claudin-5, and fibrinogen), and neuroinflammation (ICAM-1, Iba-1, and GFAP) were investigated. Results: Robust development of CMH in the inflammation-induced and CAA-associated spontaneous mouse models was observed. Inflammation-induced CMH were associated with markers of BBB dysfunction and inflammation, and CAA-associated spontaneous CMH were associated primarily with markers of neuroinflammation. Genetic deletion of the PDE3A gene did not alter BBB function, microglial activation, or CMH development, but significantly reduced endothelial and astrocyte activation in the inflammation-induced CMH mouse model. In the CAA-associated CMH mouse model, PDE3A modulation via pharmacological inhibition by cilostazol did not alter BBB function, neuroinflammation, or CMH development. Conclusions: Modulation of the PDE3A pathway, either by genetic deletion or pharmacological inhibition, does not alter CMH development in an inflammation-induced or in a CAA-associated mouse model of CMH. The role of microglial activation and BBB injury in CMH development warrants further investigation

A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression

In T cells, the Tec kinases IL-2-inducible T cell kinase (ITK) and resting lymphocyte kinase (RLK) are activated by TCR stimulation and are required for optimal downstream signaling. Studies of CD4(+) T cells from Itk(-/-) and Itk(-/-)Rlk(-/-) mice have indicated differential roles of ITK and RLK in Th1, Th2, and Th17 differentiation and cytokine production. However, these findings are confounded by the complex T cell developmental defects in these mice. In this study, we examine the consequences of ITK and RLK inhibition using a highly selective and potent small molecule covalent inhibitor PRN694. In vitro Th polarization experiments indicate that PRN694 is a potent inhibitor of Th1 and Th17 differentiation and cytokine production. Using a T cell adoptive transfer model of colitis, we find that in vivo administration of PRN694 markedly reduces disease progression, T cell infiltration into the intestinal lamina propria, and IFN-gamma production by colitogenic CD4(+) T cells. Consistent with these findings, Th1 and Th17 cells differentiated in the presence of PRN694 show reduced P-selectin binding and impaired migration to CXCL11 and CCL20, respectively. Taken together, these data indicate that ITK plus RLK inhibition may have therapeutic potential in Th1-mediated inflammatory diseases

Aging Exacerbates Development of Cerebral Microbleeds in a Mouse Model

Background: Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age. Methods: We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. Seven days after the first LPS/saline injection, brains were harvested, sectioned, and stained with hematoxylin and eosin (H&E) and Prussian blue (PB) to estimate acute/fresh and sub-acute CMH development, respectively. The relationships between microglial/macrophage activation (ionized calcium-binding adapter molecule-1), astrocyte activation (glial fibrillary acidic protein), blood-brain barrier (BBB) disruption (brain immunoglobulin G), aging, and CMH development were examined using immunohistochemistry. Results: Aging alone did not increase spontaneous H&E-positive CMH development but significantly increased the number, size, and total area of LPS-induced H&E-positive CMH in mice. LPS- and saline-treated aged mice had significantly larger PB-positive CMH compared with young mice, but the total area of PB-positive CMH was increased only in LPS-treated aged mice. Aged mice had significantly increased microglial/macrophage activation, which correlated with H&E- and PB-positive CMH development. Aged mice treated with LPS had significantly increased astrocyte activation and BBB disruption compared with young LPS-treated mice. Conclusions: Aging makes the brain more susceptible to inflammation-induced CMH in mice, and this increase in CMH with aging is associated with microglial/macrophage activation

Plasmas and Controlled Nuclear Fusion

Contains reports on three research projects.National Science Foundation (Grant GK-57)National Science Foundation (Grant GK-1165

Developmental appearance of factors that bind specifically to cis-regulatory sequences of a gene expressed in the sea urchin embryo

Previous gene-transfer experiments have identified a 2500-nucleotide 5' domain of the CyIIIa cytoskeletal actin gene, which contains cis-regulatory sequences that are necessary and sufficient for spatial and temporal control of CyIIIa gene expression during embryogenesis. This gene is activated in late cleavage, exclusively in aboral ectoderm cell lineages. In this study, we focus on interactions demonstrated in vitro between sequences of the regulatory domain and proteins present in crude extracts derived from sea urchin embryo nuclei and from unfertilized eggs. Quantitative gel-shift measurements are utilized to estimate minimum numbers of factor molecules per embryo at 24 hr postfertilization, when the CyIIIa gene is active, at 7 hr, when it is still silent, and in the unfertilized egg. We also estimate the binding affinity preferences (K_r) of the various factors for their respective sites, relative to their affinity for synthetic DNA competitors. At least 14 different specific interactions occur within the regulatory regions, some of which produce multiple DNA-protein complexes. Values of K_r range from approximately 2 x 10^4 to approximately 2 x 10^6 for these factors under the conditions applied. With one exception, the minimum factor prevalences that we measured in the 400-cell 24-hr embryo nuclear extracts fell within the range of 2 x 10^5 to 2 x 10^6 molecules per embryo, i.e., a few hundred to a few thousand molecules per nucleus. Three developmental patterns were observed with respect to factor prevalence: Factors reacting at one site were found in unfertilized egg cytoplasm at about the same level per egg or embryo as in 24-hr embryo nuclei; factors reacting with five other regions of the regulatory domain are not detectable in egg cytoplasm but in 7-hr mid-cleavage-stage embryo, nuclei are already at or close to their concentrations in the 24-hr embryo nuclei; and factors reacting with five additional regions are not detectable in egg cytoplasm and are low in 7-hr embryo nuclei, i.e., ⩽10% per embryo of the level they attain in 24-hr embryo nuclei. The rise in concentration of factors of the latter class could provide the proximal cause for the temporal activation of the CyIIIa gene at the early blastula stage