Steve Kane

Grism-pair stretcher–compressor system for simultaneous second- and third-order dispersion compensation in chirped-pulse amplification

We present a grating pair based on Carpenter prisms whose third-order dispersion is opposite that of a traditional grating pair. A properly designed stretcher–compressor system with these gratings has the unique characteristic that it simultaneously compensates for second- and third-order dispersion as a function of grating separation, as opposed to traditional systems, which require an additional grating angle mismatch. The applicability of this design to 30-fs, millijoule-level chirped-pulse amplification is discussed.

Chirped-pulse amplification of 55-fs pulses at a 1-kHz repetition rate in a Ti:Al2O3 regenerative amplifier.

40-fs pulses are stretched to 372 ps by an all-reflective-optics stretcher with 1200-line/mm holographic gratings and are then amplified to an energy of 0.7 mJ in a regenerative amplifier. After compression, 0.35-mJ, 55-fs transform-limited pulses are produced.

Grating compensation of third-order material dispersion in the normal dispersion regime: Sub-100-fs chirped-pulse amplification using a fiber stretcher and grating-pair compressor

We describe a method for compensating large amounts of second- and third-order material dispersion, and we present two simple, compact and robust stretcher-compressor systems for microjoule-and millijoule-level chirped-pulse amplification. These systems, which use dispersive material to stretch and a modified grating pair to compress the pulse, provide expansion and compression with full cubic-phase compensation. Unlike previous fiber-stretcher systems which were limited to picosecond pulse durations, these systems can be used effectively with 50-fs microjoule pulses or 100-fs millijoule pulses. The results of our model are described, including the quartic-phase limitations for both systems. We discuss other applications of this grating pair to other areas of ultrafast optics, including intracavity dispersion compensation for femtosecond oscillators. >

Efficient reflection grisms for pulse compression and dispersion compensation of femtosecond pulses

Efficient reflection grisms for pulse-compression and material-dispersion compensation have been designed and demonstrated in a 40 fs, 300 microJ, 5 kHz downchirped pulse amplification system for the first time to our knowledge. A grism design for 800 nm femtosecond laser pulse dispersion compensation applications is realized by using standard, commercial diffraction gratings.

Fourth-order-dispersion limitations of aberration-free chirped-pulse amplification systems

To obtain shorter pulses in chirped-pulse-amplification lasers, researchers have recently proposed several designs for aberration-free pulse stretchers. We examine the limitations of two aberration-free chirped-pulse-amplification systems and show that comparable results can be obtained with simpler, conventional pulse stretchers. In addition, we present a simple, quintic-phase-limited, aberration-free chirped-pulse-amplification system that can support ultrashort, high-contrast pulses.

Terawatt Ti:sapphire laser with a spherical reflective-optic pulse expander

We have developed a novel stretcher-compressor system to produce 45-fs, 75-mJ pulses at a 10-Hz repetition rate.

Compensation of self-phase modulation in chirped-pulse amplification laser systems.

Small amounts of self-phase modulation can lead to significant pulse distortions in chirped-pulse amplifiers. However, we show the surprising result that the strong chirp of the pulse can be exploited to remove these distortions completely by linear pulse shaping before amplification.

PTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE2-Mediated Inhibition of Phagocytosis of Fungi

By promoting actin depolymerization, the protein phosphatase activity of PTEN impairs macrophage phagocytosis of a fungal pathogen. Preventing Phagocytosis The fungus Candida albicans is normally a commensal microbe found on mucosal surfaces, including those in the lung. However, C. albicans can cause systemic infections that are a leading cause of morbidity and mortality in immunocompromised individuals. A key innate immune response to C. albicans is its ingestion (phagocytosis) by macrophages, a process that requires polymerization of the actin cytoskeleton. Another component of the macrophage response to fungus is the production of prostaglandin E2 (PGE2), a lipid mediator whose synthesis is initiated by cyclooxygenase (COX) enzymes. Serezani et al. found that infection of alveolar macrophages with C. albicans triggered the production of PGE2, which prevented polymerization of the actin cytoskeleton and inhibited phagocytosis of C. albicans by alveolar macrophages. The authors defined the signaling pathway involved. These results suggest that COX inhibitors, such as aspirin, which are in widespread clinical use, may stimulate innate immune responses. In addition, immunosuppression is associated with increased production of PGE2, which may help to explain how antifungal responses are attenuated in immunocompromised individuals. Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E2 (PGE2) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE2-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE2 suppressed phagocytosis and F-actin formation through the PGE2 receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE2. PGE2-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE2 accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.

Leukotrienes target F-actin/cofilin-1 to enhance alveolar macrophage anti-fungal activity

Candida albicans is the most common opportunistic fungal pathogen and causes local and systemic disease in immunocompromised patients. Alveolar macrophages (AMs) are pivotal for the clearance of C. albicans from the lung. Activated AMs secrete 5-lipoxygenase-derived leukotrienes (LTs), which in turn enhance phagocytosis and microbicidal activity against a diverse array of pathogens. Our aim was to investigate the role of LTB4 and LTD4 in AM antimicrobial functions against C. albicans and the signaling pathways involved. Pharmacologic and genetic inhibition of LT biosynthesis as well as receptor antagonism reduced phagocytosis of C. albicans when compared with untreated or WT controls. Conversely, exogenous LTs of both classes augmented base-line C. albicans phagocytosis by AMs. Although LTB4 enhanced mainly mannose receptor-dependent fungal ingestion, LTD4 enhanced mainly dectin-1 receptor-mediated phagocytosis. LT enhancement of yeast ingestion was dependent on protein kinase C-δ (PKCδ) and PI3K but not PKCα and MAPK activation. Both LTs reduced activation of cofilin-1, whereas they enhanced total cellular F-actin; however, LTB4 accomplished this through the activation of LIM kinases (LIMKs) 1 and 2, whereas LTD4 did so exclusively via LIMK-2. Finally, both exogenous LTB4 and LTD4 enhanced AM fungicidal activity in an NADPH oxidase-dependent manner. Our data identify LTB4 and LTD4 as key mediators of innate immunity against C. albicans, which act by both distinct and conserved signaling mechanisms to enhance multiple antimicrobial functions of AMs.

Macrophage Dectin-1 Expression Is Controlled by Leukotriene B4 via a GM-CSF/PU.1 Axis

Pattern recognition receptors for fungi include dectin-1 and mannose receptor, and these mediate phagocytosis, as well as production of cytokines, reactive oxygen species, and the lipid mediator leukotriene B4 (LTB4). The influence of G protein-coupled receptor ligands such as LTB4 on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB4 signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB4 production and signaling through its high-affinity G protein-coupled receptor leukotriene B4 receptor 1 (BLT1) direct dectin-1–dependent binding, ingestion, and cytokine production both in vitro and in vivo. Impaired responses to fungal glucans correlated with lower dectin-1 expression in macrophages from leukotriene (LT)- and BLT1-deficent mice than their wild-type counterparts. LTB4 increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB4-enhanced dectin-1 expression. GM-CSF controls PU.1 expression, and this cytokine was decreased in LT-deficient macrophages. Addition of GM-CSF to LT-deficient cells restored expression of dectin-1 and PU.1, as well as dectin-1 responsiveness. In addition, LTB4 effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF−/− macrophages. Our results identify LTB4-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses.