Laser-plasma accelerators of only a centimetre’s length have produced nearly monoenergetic electron bunches with energy as high as 1 GeV. Scaling these compact accelerators to multi-gigaelectronvolt energy would open the prospect of building X-ray free-electron lasers and linear colliders hundreds of times smaller than conventional facilities, but the 1 GeV barrier has so far proven insurmountable. Here, by applying new petawatt laser technology, we produce electron bunches with a spectrum prominently peaked at 2 GeV with only a few per cent energy spread and unprecedented sub-milliradian divergence. Petawatt pulses inject ambient plasma electrons into the laser-driven accelerator at much lower density than was previously possible, thereby overcoming the principal physical barriers to multi-gigaelectronvolt acceleration: dephasing between laser-driven wake and accelerating electrons and laser pulse erosion. Simulations indicate that with improvements in the laser-pulse focus quality, acceleration to nearly 10 GeV should be possible with the available pulse energy.

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15-Deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a cyclopentenone prostaglandin, displays a potent anti-inflammatory effect at micromolar concentrations (>2 M) through direct inhibition of nuclear factor (NF)-B activation. Here we show that at submicromolar concentrations (0.1-0.5 M) 15d-PGJ 2 retains the ability to suppress the production of tumor necrosis factor-␣ (TNF-␣) and nitric oxide (NO) in lipopolysaccharide (LPS)-activated murine J774 macrophages under the conditions of a prolonged incubation (>12 h). Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti-inflammatory action of 15d-PGJ 2 . Inhibition of HO-1 activity or scavenging carbon monoxide (CO), a byproduct derived from heme degradation, significantly attenuated the suppressive activity of 15d-PGJ 2 . Furthermore, LPS-induced NF-B activation assessed by the inhibitory protein of NF-B (I B) degradation and p50 nuclear translocation was diminished in cells subjected to prolonged treatment with the low concentration of 15d-PGJ 2 . Treatment of cells with the protein synthesis inhibitor, cycloheximide, or the specific p38 MAP kinase inhibitor, SB203580, blocked the induction of HO-1 and suppression of LPS-induced I B degradation mediated by 15d-PGJ 2 . Likewise, HO inhibitor and CO scavenger were effective in abolishing the inhibitory effects of 15d-PGJ 2 on NF-B activation induced by LPS. The functional role of CO was further demonstrated by the use of a CO releasing molecule, tricarbonyldichlororuthenium(II) dimer, which significantly suppressed LPS-induced nuclear translocation of p50 as assessed by confocal immunofluorescence. Collectively, these data suggest that even at submicromolar concentrations 15d-PGJ 2 can exert an anti-inflammatory effect in macrophages through a mechanism that involves the action of HO/CO.15-Deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), 1 a dehydration product of prostaglandin D 2 , has been shown to be present in the inflammatory exudates and is increased during the resolution phase of inflammation (1). The biological effects of 15d-PGJ 2 have attracted considerable interest in recent years. It was initially identified as a high affinity natural ligand for the peroxisome proliferator-activated receptor-␥ (PPAR␥) and shown to exert several effects through binding to this nuclear receptor (2-5). More recently, several recent studies have shown that 15d-PGJ 2 exhibits a potent anti-inflammatory effect by attenuating the expression of proinflammatory mediators in activated monocytes/macrophages mainly through the inhibition of NF-B-dependent transcription of inflammatory genes (6, 7). In addition to antagonizing the NF-B activity through PPAR␥-dependent mechanism (6 -8), 15d-PGJ 2 can directly inhibit the signaling steps leading to NF-B activation (9 -12). It has also been shown that the ␣,␤-unsaturated carbonyl group of 15d-PGJ 2 can act as an electrophile to react covalently with specific cysteine residues located in the activa...

The pro-oxidative properties of the four flavonoids, quercetin, morin, naringenin and hesperetin, in human lymphocyte system were investigated. Naringenin and hesperetin accelerated the oxidation of deoxyribose induced by Fe(3+)/H(2)O(2) in a concentration range of 0-200 microM, but quercetin and morin decreased it when the concentration was greater than 100 microM. The generation of hydrogen peroxide and the superoxide anion and the production of TBARS in lymphocytes were increased with increasing concentration of a flavonoid. Cell membrane protein thiols of the lymphocytes decreased when treated with the four flavonoids. Quercetin and hesperetin had no significant effect (p>0.05) on the activity of glutathione reductase, but morin and naringenin could inhibit the activity of the enzyme at a concentration of 200 microM, when compared to the control group. The glutathione S-transferase activity was slightly decreased by treatment with each of the four flavonoids only at a concentration of 200 microM. Therefore, the DNA damage in lymphocytes induced by the flavonoids in the model system might have been due to their stimulation of oxidative stress in the lymphocytes, which resulted in the decrease of cell membrane protein thiols, increase of lipid peroxidation in cell membrane and in the influence of the antioxidative enzyme activities.

We present an in-depth experimental-computational study of the parameters necessary to optimize a tunable, quasi-monoenergetic, efficient, low-background Compton backscattering (CBS) x-ray source that is based on the self-aligned combination of a laser-plasma accelerator (LPA) and a plasma mirror (PM). The main findings are: (1) an LPA driven in the blowout regime by 30 TW, 30 fs laser pulses producesnot only a highquality, tunable, quasi-monoenergetic electron beam, but also a high-quality, relativistically intense (a 0 ∼ 1) spent drive pulse that remains stable in profile and intensity over the LPA tuning range. (2) A thin plastic film near the gas jet exit retro-reflects the spent drive pulse efficiently into oncoming electrons to produce CBS x-rays without detectable bremsstrahlung background. Meanwhile anomalous far-field divergence of the retro-reflected light demonstrates relativistic "denting" of the PM. Exploiting these optimized LPA and PM conditions, we demonstrate quasi-monoenergetic (50% FWHM energy spread), tunable (75 to 200 KeV) CBS x-rays, characteristics previously achieved only on more powerful laser systems by CBS of a split-off, counter-propagating pulse. Moreover, laser-to-x-ray photon conversion efficiency (∼ 6 × 10 −12 ) exceeds that of any previous LPA-based quasi-monoenergetic Compton source. Particle-in-cell simulations agree well with the measurements.