Diagnosis of ultrafast surface dynamics of thin foil targets irradiated by intense laser pulses.

The temporal modulation of an electron bunch train accelerated from a foil target irradiated by an intense laser pulse is studied by measuring the coherent transition radiation (CTR) from the rear surface of a target. We experimentally obtained CTR spectra from a 1 µm thick foil target irradiated at a maximum intensity of 6.5 × 1019 W/cm2. Spectral redshifts of the emitted radiation corresponding to increases in laser intensity were observed. These measurements were compared with the theoretical calculation of CTR spectra considering ultrafast surface dynamics, such as plasma surface oscillation and relativistically induced transparency. Plasma surface oscillations induce a spectral redshift, while relativistic transparency causes a spectral blueshift. Both effects are required to find reasonable agreement with the experiment over the entire range of laser intensities.

Fungal peri-prosthetic joint infection after primary total knee replacement.

We retrospectively reviewed 30 two-stage revision procedures in 28 patients performed for fungal peri-prosthetic joint infection (PJI) after a primary total knee replacement. Patients were followed for at least two years or until the infection recurred. The mean follow-up for patients who remained free of infection was 4.3 years (2.3 to 6.1). Overall, 17 patients were assessed as American Society of Anesthesiologists grade 3 or 4. The surgical protocol included removal of the infected implant, vigorous debridement and insertion of an articulating cement spacer. This was followed by at least six weeks of antimicrobial treatment and delayed reimplantation in all patients. The mean interval between removal of the prosthesis and reimplantation was 9.5 weeks (6 to 24). After reimplantation, patients took antifungal agents orally for a maximum of six months. Two knees became reinfected at one and two months post-operatively, respectively: one of these subsequently required arthrodesis because of uncontrolled infection. Fungal PJIs can be treated successfully by removal of all infected material, appropriate antimicrobial treatment and delayed reimplantation.

An antibody inhibitor of the LMO2-protein complex blocks its normal and tumorigenic functions.

The LIM-domain protein LMO2 is a T-cell oncogenic protein first recognized by gene activation through chromosomal translocations, but it is also responsible for leukaemias arising as secondary, adverse effects in an X-SCID gene therapy trial. There are no specific reagents currently available to analyse the LMO2 multiprotein complex or to combat LMO2-dependent leukaemias. Accordingly, we have isolated an anti-LMO2 single chain Fv antibody fragment to determine if intracellular interference with LMO2-protein complexes can avert LMO2-dependent functions in normal and cancer settings. The anti-LMO2 single chain Fv, obtained using Intracellular Antibody Capture (IAC) technology, is specific for LMO2 among the LIM-only protein family and binds LMO2 through the third and fourth LIM fingers. Using vector-mediated expression of anti-LMO2 scFv, we show inhibition of Lmo2-dependent erythropoiesis but not endothelial development. We also demonstrate inhibition of Lmo2-dependent leukaemia in a mouse T-cell tumourigenesis transplantation assay with retroviral-mediated expression of anti-LMO2 scFv. Our studies establish that interference with the LMO2 multiprotein complex inhibits both normal and tumourigenic roles. The antibody fragment is a tool for dissecting LMO2 function in haematopoiesis and leukaemia and is a lead for development of therapeutics against LMO2-dependent T-ALL.

Chromosomal translocation engineering to recapitulate primary events of human cancer.

Mouse models of human cancers are important for understanding determinants of overt disease and for "preclinical" development of rational therapeutic strategies; for instance, based on macrodrugs. Chromosomal translocations underlie many human leukemias, sarcomas, and epithelial tumors. We have developed three technologies based on homologous recombination in mouse ES cells to mimic human chromosome translocations. The first, called the knockin method, allows creation of fusion genes like those typical of translocations of human leukemias and sarcomas. Two new conditional chromosomal translocation mimics have been developed. The first is a method for generating reciprocal chromosomal translocations de novo using Cre-loxP recombination (translocator mice). In some cases, there is incompatible gene orientation and the translocator model cannot be applied. We have developed a different model (invertor mice) for these situations. This method consists of introducing an inverted cDNA cassette into the intron of a target gene and bringing the cassette into the correct transcriptional orientation by Cre-loxP recombination. We describe experiments using the translocator model to generate MLL-mediated neoplasias and the invertor method to generate EWS-ERG-mediated cancer. These methods mimic the situation found in human chromosome translocations and provide the framework for design and study of human chromosomal translocations in mice.

Wave-front phase measurements of high-order harmonic beams by use of point-diffraction interferometry.

We report the wave-front phase measurement of high-order harmonics employing point-diffraction interferometry. The high-order harmonics generated in a gas-filled hollow tube showed excellent spatial coherence over nearly the whole cross section of the harmonic beams. Using this coherent harmonic source in the extreme-ultraviolet-soft-x-ray region, we have demonstrated the operation of a point-diffraction interferometer and measured the wave-front phase of high-order harmonics.

Emission of a hot electron jet from intense femtosecond-laser-cluster interactions.

A directional hot electron jet with energy higher than 100 keV was generated along the laser propagation direction from Ar clusters irradiated with a laser pulse of duration 28 fs and intensity 1 x 10(17) W/cm(2). The hot electron jet was detected only with linearly polarized laser pulses, not with circularly polarized pulses. Channel betatron resonance is believed to be the main accelerating mechanism for this directional hot electron jet.

Coherent control of high-order harmonics with chirped femtosecond laser pulses.

High-order harmonics were coherently controlled using chirped femtosecond laser pulses for the production of sharp and strong harmonics. As the laser intensity was increased above the saturation intensity for optical-field ionization, the laser chirp needed to suppress harmonic chirp in the plateau region changed from positive to negative. We showed that the modification of a laser chirp condition in a rapidly ionizing medium should be included for the proper coherent control of high-order harmonics, necessitating the integral treatment of the interaction between atoms and a driving laser pulse.

Space-resolving flat-field extreme ultraviolet spectrograph system and its aberration analysis with wave-front aberration.

The Nam aberration of a flat-field extreme ultraviolet spectrograph system, composed of a varied line-spacing concave grating and a toroidal mirror, was analyzed by calculating the wave-front aberration with respect to an astigmatic reference surface. The toroidal mirror was used to compensate for the astigmatism that was due to the grazing incidence of light at the concave grating. The spectrograph system could form a space-resolved spectrum along the sagittal direction. The spectral and spatial resolutions of the spectrograph system were estimated from the root-mean-square spot size. The actual spectral resolution of the spectrograph system was measured from extreme ultraviolet spectra obtained from plasmas produced by an iodine laser having an energy of 0.5 J in a 4-ns duration, and it was compared with the calculated value.

Significant improvement in the efficiency and brightness of the J = 0-1 19.6-nm line of the germanium laser by use of double-pulse pumping.

We describe significant improvement in the efficiency and brightness of the J = 0-1 19.6-nm line of the neonlike germanium laser. A curved slab target was irradiated by two laser pulses of 100-ps duration separated by 300 ps with a total energy of 200-300 J on target. Compared with that obtained by 1-ns single-pulse pumping with 1.1 kJ of energy, the J = 0-1 line has a 12 times higher peak intensity, with a smaller beam divergence of 2 mrad, corresponding to a factor-of-25 improvement in brightness.