Outflows and the Physical Properties of Quasars

We have investigated a sample of 5088 quasars from the Sloan Digital Sky Survey Second Data Release in order to determine how the frequency and properties of broad absorptions lines (BALs) depend on black hole mass, bolometric luminosity, Eddington fraction (L/L_Edd), and spectral slope. We focus only on high-ionization BALs and find a number of significant results. While quasars accreting near the Eddington limit are more likely to show BALs than lower $L/L_{Edd}$ systems, BALs are present in quasars accreting at only a few percent Eddington. We find a stronger effect with bolometric luminosity, such that the most luminous quasars are more likely to show BALs. There is an additional effect, previously known, that BAL quasars are redder on average than unabsorbed quasars. The strongest effects involving the quasar physical properties and BAL properties are related to terminal outflow velocity. Maximum observed outflow velocities increase with both the bolometric luminosity and the blueness of the spectral slope, suggesting that the ultraviolet luminosity to a great extent determines the acceleration. These results support the idea of outflow acceleration via ultraviolet line scattering.Comment: Uses emulateapj.cls, 14 pages including 7 tables and 7 figures. Accepted for publication in the Astrophysical Journal, Unabridged version of Table 4 can be downloaded from http://physics.uwyo.edu/agn

Platelet CD36 Signaling Through ERK5 Promotes Caspase-Dependent Procoagulant Activity and Fibrin Deposition In Vivo

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients

Platelet CD36 promotes thrombosis by activating redox sensor ERK5 in hyperlipidemic conditions

Atherothrombosis is a process mediated by dysregulated platelet activation that can cause life-threatening complications and is the leading cause of death by cardiovascular disease. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein (oxLDL) particles, a process that induces an overt prothrombotic phenotype. The mechanisms by which CD36 promotes platelet activation and thrombosis remain incompletely defined. In this study, we identify a mechanism for CD36 to promote thrombosis by increasing activation of MAPK extracellular signal-regulated kinase 5 (ERK5), a protein kinase known to be exquisitely sensitive to redox stress, through a signaling pathway requiring Src kinases, NADPH oxidase, superoxide radical anion, and hydrogen peroxide. Pharmacologic inhibitors of ERK5 blunted platelet activation and aggregation in response to oxLDL and targeted genetic deletion of ERK5 in murine platelets prevented oxLDL-induced platelet deposition on immobilized collagen in response to arterial shear. Importantly, in vivo thrombosis experiments after bone marrow transplantation from platelet-specific ERK5 null mice into hyperlipidemic apolipoprotein E null mice showed decreased platelet accumulation and increased thrombosis times compared with mice transplanted with ERK5 expressing control bone marrows. These findings suggest that atherogenic conditions critically regulate platelet CD36 signaling by increasing superoxide radical anion and hydrogen peroxide through a mechanism that promotes activation of MAPK ERK5