Investigating the impact of reservoir properties and injection parameters on carbon dioxide dissolution in saline aquifers

CO2 injection into geological formations is considered one way of mitigating the increasing levels of carbon dioxide concentrations in the atmosphere and its effect on and global warming. In regard to sequestering carbon underground, different countries have conducted projects at commercial scale or pilot scale and some have plans to develop potential storage geological formations for carbon dioxide storage. In this study, pure CO2 injection is examined on a model with the properties of bunter sandstone and then sensitivity analyses were conducted for some of the fluid, rock and injection parameters. The results of this study show that the extent to which CO2 has been convected in the porous media in the reservoir plays a vital role in improving the CO2 dissolution in brine and safety of its long term storage. We conclude that heterogeneous permeability plays a crucial role on the saturation distribution and can increase or decrease the amount of dissolved CO2 in water around ± 7% after the injection stops and up to 13% after 120 years. Furthermore, the value of absolute permeability controls the effect of the Kv/Kh ratio on the CO2 dissolution in brine. In other words, as the value of vertical and horizontal permeability decreases (i.e., tight reservoirs) the impact of Kv/Kh ratio on the dissolved CO2 in brine becomes more prominent. Additionally, reservoir engineering parameters, such as well location, injection rate and scenarios, also have a high impact on the amount of dissolved CO2 and can change the dissolution up to 26%, 100% and 5.5%, respectively

Transverse Spin Structure of the Nucleon through Target Single Spin Asymmetry in Semi-Inclusive Deep-Inelastic (e,e′π±)(e,e^\prime \pi^\pm) Reaction at Jefferson Lab

Jefferson Lab (JLab) 12 GeV energy upgrade provides a golden opportunity to perform precision studies of the transverse spin and transverse-momentum-dependent structure in the valence quark region for both the proton and the neutron. In this paper, we focus our discussion on a recently approved experiment on the neutron as an example of the precision studies planned at JLab. The new experiment will perform precision measurements of target Single Spin Asymmetries (SSA) from semi-inclusive electro-production of charged pions from a 40-cm long transversely polarized $^3$He target in Deep-Inelastic-Scattering kinematics using 11 and 8.8 GeV electron beams. This new coincidence experiment in Hall A will employ a newly proposed solenoid spectrometer (SoLID). The large acceptance spectrometer and the high polarized luminosity will provide precise 4-D ($x$, $z$, $P_T$ and $Q^2$) data on the Collins, Sivers, and pretzelocity asymmetries for the neutron through the azimuthal angular dependence. The full 2$\pi$ azimuthal angular coverage in the lab is essential in controlling the systematic uncertainties. The results from this experiment, when combined with the proton Collins asymmetry measurement and the Collins fragmentation function determined from the e$^+$e$^-$ collision data, will allow for a quark flavor separation in order to achieve a determination of the tensor charge of the d quark to a 10% accuracy. The extracted Sivers and pretzelocity asymmetries will provide important information to understand the correlations between the quark orbital angular momentum and the nucleon spin and between the quark spin and nucleon spin.Comment: 23 pages, 13 figures, minor corrections, matches published versio

Lung-derived macrophage migration inhibitory factor in adult patients with septic shock, and its role in cardiocirculatory depression

Migration inhibitory factor (MIF), a critical proinflammatory mediator in sepsis, has a profound affect on cardiovascular function. Our animal studies show that the lungs release MIF into the systemic circulation during late sepsis. MIF released in this way has direct and immediate access to cardiac cells. The purpose of our study was to assess the lung as a source of MIF in human septic shock patients and to further study the MIF-associated pathways involved in cardiovascular depression

Nicotinic Acetylcholine Receptor Agonists Attenuate Septic Acute Kidney Injury in Mice by Suppressing Inflammation and Proteasome Activity

Sepsis is one of the leading causes of acute kidney injury (AKI). Septic patients who develop acute kidney injury (AKI) are at increased risk of death. To date there is no effective treatment for AKI or septic AKI. Based on their anti-inflammatory properties, we examined the effects of nicotinic acetylcholine receptor agonists on renal damage using a mouse model of lipopolysaccharide (LPS)-induced AKI where localized LPS promotes inflammation-mediated kidney damage. Administration of nicotine (1 mg/kg) or GTS-21 (4 mg/kg) significantly abrogated renal leukocyte infiltration (by 40%) and attenuated kidney injury. These renoprotective effects were accompanied by reduced systemic and localized kidney inflammation during LPS-induced AKI. Consistent with these observations, nicotinic agonist treatment significantly decreased renal IκBα degradation and NFκB activation during LPS-induced AKI. Treatment of human kidney cells with nicotinic agonists, an NFκB inhibitor (Bay11), or a proteasome inhibitor (MG132) effectively inhibited their inflammatory responses following stimulation with LPS or TNFα. Renal proteasome activity, a major regulator of NFκB-mediated inflammation, was enhanced by approximately 50% during LPS-induced AKI and elevated proteasome activity was significantly blunted by nicotinic agonist administration in vivo. Taken together, our results identify enhanced renal proteasome activity during LPS-induced AKI and the suppression of both proteasome activity and inflammation by nicotinic agonists to attenuate LPS-induced kidney injury

Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation

Endothelial cell activation plays a critical role in regulating leukocyte recruitment during inflammation and infection. Based on recent studies showing that acetylcholine and other cholinergic mediators suppress the production of proinflammatory cytokines via the α7 nicotinic acetylcholine receptor (α7 nAChR) expressed by macrophages and our observations that human microvascular endothelial cells express the α7 nAChR, we examined the effect of cholinergic stimulation on endothelial cell activation in vitro and in vivo. Using the Shwartzman reaction, we observed that nicotine (2 mg/kg) and the novel cholinergic agent CAP55 (12 mg/kg) inhibit endothelial cell adhesion molecule expression. Using endothelial cell cultures, we observed the direct inhibitory effects of acetylcholine and cholinergic agents on tumor necrosis factor (TNF)-induced endothelial cell activation. Mecamylamine, an nAChR antagonist, reversed the inhibition of endothelial cell activation by both cholinergic agonists, confirming the antiinflammatory role of the nAChR cholinergic pathway. In vitro mechanistic studies revealed that nicotine blocked TNF-induced nuclear factor–κB nuclear entry in an inhibitor κB (IκB)α- and IκBɛ-dependent manner. Finally, with the carrageenan air pouch model, both vagus nerve stimulation and cholinergic agonists significantly blocked leukocyte migration in vivo. These findings identify the endothelium, a key regulator of leukocyte trafficking during inflammation, as a target of anti-inflammatory cholinergic mediators

ISO-1 Binding to the Tautomerase Active Site of MIF Inhibits Its Pro-inflammatory Activity and Increases Survival in Severe Sepsis

MIF is a proinflammatory cytokine that has been implicated in the pathogenesis of sepsis, arthritis, and other inflammatory diseases. Antibodies against MIF are effective in experimental models of inflammation, and there is interest in strategies to inhibit its deleterious cytokine activities. Here we identify a mechanism of inhibiting MIF pro-inflammatory activities by targeting MIF tautomerase activity. We designed small molecules to inhibit this tautomerase activity; a lead molecule, "ISO-1 ((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester)," significantly inhibits the cytokine activity in vitro. Moreover, ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages. The therapeutic importance of the MIF inhibition by ISO-1 is demonstrated by the significant protection from sepsis, induced by cecal ligation and puncture in a clinically relevant time frame. These results identify ISO-1 as the first small molecule inhibitor of MIF proinflammatory activities with therapeutic implications and indicate the potential of the MIF active site as a novel target for therapeutic interventions in human sepsis

Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF (TNF alpha) levels in murine endotoxemia. This effect was recapitulated by peripheral administration of the compound. BQCA also improved survival in murine endotoxemia and these effects were abolished in M1 mAChR knockout (KO) mice. Selective optogenetic stimulation of basal forebrain cholinergic neurons innervating brain regions with abundant M1 mAChR localization reduced serum TNF in endotoxemic mice. These findings reveal that forebrain cholinergic neurons regulate innate immune responses and inflammation, suggesting the possibility that in diseases associated with cholinergic dysfunction, including Alzheimer\u27s disease this anti-inflammatory regulation can be impaired. These results also suggest novel anti-inflammatory approaches based on targeting forebrain cholinergic signaling in sepsis and other disorders characterized by immune dysregulation