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Passive immunotherapy is a very promising approach for the treatment of Alzheimer's disease (AD). Among the different antibodies under development, those targeting post-translationally modified Aβ peptides might combine efficient reduction in beta-amyloid accompanied by lower sequestration in peripheral compartments and thus anticipated and reduced treatment-related side effects. In that regard, we recently demonstrated that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to the attenuation of AD-like amyloid pathology in 5xFAD mice. In order to assess novel strategies to enhance the efficacy of passive vaccination approaches, we investigated the role of CD33 for Aβ phagocytosis in transgenic mice treated with an isoD7-Aβ antibody. We crossbred 5xFAD transgenic mice with CD33 knock out (CD33KO) mice and compared the amyloid pathology in the different genotypes of the crossbreds. The knockout of CD33 in 5xFAD mice leads to a significant reduction in Aβ plaques and concomitant rescue of behavioral deficits. Passive immunotherapy of 5xFAD/CD33KO showed a significant increase in plaque-surrounding microglia compared to 5xFAD treated with the antibody. Additionally, we observed a stronger lowering of Aβ plaque load after passive immunotherapy in 5xFAD/CD33KO mice. The data suggest an additive effect of passive immunotherapy and CD33KO in terms of lowering Aβ pathology. Hence, a combination of CD33 antagonists and monoclonal antibodies might represent a strategy to enhance efficacy of passive immunotherapy in AD.

We sought to describe incidental imaging features of increased intrapericardial pressure due to pericardial effusion on chest computed tomography (CT) and correlate them with cardiac CT, cardiac magnetic resonance imaging, and echocardiography. It is important for the radiologist to become familiar with imaging findings of increased intrapericardial pressure in the setting of pericardial effusion when identified on chest CT. Recognizing the imaging findings of increased intrapericardial pressure can better guide the care of these patients.

We study the electronic screening mechanisms of the effective Coulomb on-site repulsion in hole-doped Sr(14)Cu(24)O(41) compared to undoped La(6)Ca(8)Cu(24)O(41) using polarization dependent high-resolution resonant inelastic x-ray scattering at Cu M edges. By measuring the energy of the effective Coulomb on-site repulsion and the spin excitations, we estimate superexchange and hopping matrix element energies along rungs and legs, respectively. Interestingly, hole doping locally screens the Coulomb on-site repulsion reducing it by as much as 25%. We suggest that the increased ratio of the electronic kinetic to the electronic correlation energy contributes to the local superexchange mediated pairing between holes.

Initiating the gain process in a free-electron laser (FEL) from an external highly coherent source of radiation is a promising way to improve the pulse properties such as temporal coherence and synchronization performance in time-resolved pump-probe experiments at FEL facilities, but this so-called "seeding" suffers from the lack of adequate sources at short wavelengths. We report on the first successful seeding at a wavelength as short as 38.2 nm, resulting in GW-level, coherent FEL radiation pulses at this wavelength as well as significant second harmonic emission at 19.1 nm. The external seed pulses are about 1 order of magnitude shorter compared to previous experiments allowing an ultimate time resolution for the investigation of dynamic processes enabling breakthroughs in ultrafast science with FELs. The seeding pulse is the 21st harmonic of an 800-nm, 15-fs (rms) laser pulse generated in an argon medium. Methods for finding the overlap of seed pulses with electron bunches in spatial, longitudinal, and spectral dimensions are discussed and results are presented. The experiment was conducted at FLASH, the FEL user facility at DESY in Hamburg, Germany.

An Yb:YAG thin-disk multipass laser amplifier system was developed operating in a 10 Hz burst operation mode with 800 µs burst duration and 100 kHz intra-burst repetition rate. Methods for the suppression of parasitic amplified spontaneous emission are presented. The average output pulse energy is up to 44.5 mJ and 820 fs compressed pulse duration. The average power of 4.45 kW during the burst is the highest reported for this type of amplifier.

We report on a Yb:YAG Innoslab laser amplifier system for generation of subpicsecond high energy pump pulses for optical parametric chirped pulse amplification (OPCPA) at high repetition rates. Pulse energies of up to 20 mJ (at 12.5 kHz) and repetition rates of up to 100 kHz were attained with pulse durations of 830 fs and average power in excess of 200 W. We further investigate the possibility to use subpicosecond pulses to derive a stable continuum in a YAG crystal for OPCPA seeding.

The imaging of hydrated biological samples - especially in the energy window of 284-540 eV, where water does not obscure the signal of soft organic matter and biologically relevant elements - is of tremendous interest for life sciences. Free-electron lasers can provide highly intense and coherent pulses, which allow single pulse imaging to overcome resolution limits set by radiation damage. One current challenge is to match both the desired energy and the intensity of the light source. We present the first images of dehydrated biological material acquired with 3rd harmonic radiation from FLASH by digital in-line zone plate holography as one step towards the vision of imaging hydrated biological material with photons in the water window. We also demonstrate the first application of ultrathin molecular sheets as suitable substrates for future free-electron laser experiments with biological samples in the form of a rat fibroblast cell and marine biofouling bacteria Cobetia marina.

We have observed the simultaneous inner-shell absorption of two extreme-ultraviolet photons by a Xe atom in an experiment performed at the short-wavelength free electron laser facility FLASH. Photoelectron spectroscopy permitted us to unambiguously identify a feature resulting from the ionization of a single electron of the 4d subshell of Xe by two photons each of energy (93±1)  eV. The feature's intensity has a quadratic dependence on the pulse energy. The results are discussed and interpreted within the framework of recent results of ion spectroscopy experiments of Xe obtained at ultrahigh irradiance in the extreme-ultraviolet regime.

We report on a high power optical parametric amplifier delivering 8 fs pulses with 6 GW peak power. The system is pumped by a fiber amplifier and operated at 96 kHz repetition rate. The average output power is as high as 6.7 W, which is the highest average power few-cycle pulse laser reported so far. When stabilizing the seed oscillator, the system delivered carrier-envelop phase stable laser pulses. Furthermore, high harmonic generation up to the 33(th) order (21.8 nm) is demonstrated in a Krypton gas jet. In addition, the scalability of the presented laser system is discussed.

We report on the performance of a 60 kHz repetition rate sub-10 fs, optical parametric chirped pulse amplifier system with 2 W average power and 3 GW peak power. This is to our knowledge the highest average power sub-10 fs kHz-amplifier system reported to date. The amplifier is conceived for applications at free electron laser facilities and is designed such to be scalable in energy and repetition rate.

Femtosecond vacuum ultraviolet (VUV) radiation provided by the free-electron laser FLASH was used for digital in-line holographic microscopy and applied to image particles, diatoms and critical point dried fibroblast cells. To realize the classical in-line Gabor geometry, a 1 microm pinhole was used as spatial filter to generate a divergent light cone with excellent pointing stability. At a fundamental wavelength of 8 nm test objects such as particles and diatoms were imaged at a spatial resolution of 620 nm. In order to demonstrate the applicability to biologically relevant systems, critical point dried rat embryonic fibroblast cells were for the first time imaged with free-electron laser radiation.

Coherent diffractive imaging for the reconstruction of a two-dimensional (2D) finite crystal structure with a single pulse train of free-electron laser radiation at 7.97 nm wavelength is demonstrated. This measurement shows an advance on traditional coherent imaging techniques by applying it to a periodic structure. It is also significant that this approach paves the way for the imaging of the class of specimens which readily form 2D, but not three-dimensional crystals. We show that the structure is reconstructed to the detected resolution, given an adequate signal-to-noise ratio.

A general theoretical approach based on the decomposition of statistical fields into a sum of independently propagating transverse modes was used for the analysis of the coherence properties of the new free-electron laser source FLASH operated at 13.7 nm wavelength. The analysis shows that several transverse modes are contributing to the total radiation field of FLASH. The results of theoretical calculations are compared with measurements using Young's double-slit experiment. The coherence lengths in the horizontal and in the vertical directions 20 m downstream from the source are estimated at 300 and 250 microm, respectively.

The temporal coherence properties of soft x-ray free electron laser pulses at FLASH are measured at 23.9 nm by interfering two time-delayed partial beams directly on a CCD camera. The partial beams are obtained by wave front beam splitting in an autocorrelator operating at photon energies from h nu = 30 to 200 eV. At zero delay a visibility of (0.63+/- 0.04) is measured. The delay of one partial beam reveals a coherence time of 6 fs at 23.9 nm. The visibility further displays a non-monotonic decay, which can be rationalized by the presence of multiple pulse structure.

Two-color multiphoton ionization of atomic helium was investigated by combining extreme ultraviolet (XUV) radiation from the Free Electron Laser in Hamburg with an intense synchronized optical laser. In the photoelectron spectrum, lines associated with direct ionization and above-threshold ionization show strong variations of their amplitudes as a function of both the intensity of the optical dressing field and the relative orientation of the linear polarization vectors of the two fields. The polarization dependence provides direct insight into the symmetry of the outgoing electrons in above-threshold ionization. In the high field regime, the monochromaticity of the XUV radiation enables the unperturbed observation of nonlinear processes in the optical field.

The interaction of intense extreme ultraviolet femtosecond laser pulses (lambda = 32.8 nm) from the FLASH free electron laser (FEL) with clusters has been investigated by means of photoelectron spectroscopy and modeled by Monte Carlo simulations. For laser intensities up to 5x10(13) W/cm(2), we find that the cluster ionization process is a sequence of direct electron emission events in a developing Coulomb field. A nanoplasma is formed only at the highest investigated power densities where ionization is frustrated due to the deep cluster potential. In contrast with earlier studies in the IR and vacuum ultraviolet spectral regime, we find no evidence for electron emission from plasma heating processes.

In a proof-of-principle experiment, we demonstrate high-resolution resonant laser excitation in the soft x-ray region at 48.6 eV of the 2 (2)S(1/2) to 2 (2)P(1/2) transition of Li-like Fe23+ ions trapped in an electron beam ion trap by using ultrabrilliant light from Free Electron Laser in Hamburg (FLASH). High precision spectroscopic studies of highly charged ions at this and upcoming x-ray lasers with an expected accuracy gain up to a factor of a thousand, become possible with our technique, thus potentially yielding fundamental insights, e.g., into basic aspects of QED.

Because of the stochastic nature of self-amplified spontaneous emission (SASE), it is crucial to measure for single pulses the spectral characteristics of ultrashort pulses from the vacuum ultraviolet free electron laser (FLASH) at DESY, Germany. To meet this particular challenge, we have employed both photon and photoelectron spectroscopy. Each FEL pulse is composed of an intense and spectrally complex fundamental, centered at a photon energy of about 38.5 eV, with a bandwidth of 0.5% accompanied by higher harmonics, each carrying an intensity of typically 0.3 to 0.6% of that of the fundamental. The correlation between the harmonics and the fundamental is in remarkable agreement with a simple statistical model of SASE FEL radiation.

Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion.

The genome of the japonica subspecies of rice, an important cereal and model monocot, was sequenced and assembled by whole-genome shotgun sequencing. The assembled sequence covers 93% of the 420-megabase genome. Gene predictions on the assembled sequence suggest that the genome contains 32,000 to 50,000 genes. Homologs of 98% of the known maize, wheat, and barley proteins are found in rice. Synteny and gene homology between rice and the other cereal genomes are extensive, whereas synteny with Arabidopsis is limited. Assignment of candidate rice orthologs to Arabidopsis genes is possible in many cases. The rice genome sequence provides a foundation for the improvement of cereals, our most important crops.

Experimental results are presented from vacuum-ultraviolet free-electron laser (FEL) operating in the self-amplified spontaneous emission (SASE) mode. The generation of ultrashort radiation pulses became possible due to specific tailoring of the bunch charge distribution. A complete characterization of the linear and nonlinear modes of the SASE FEL operation was performed. At saturation the FEL produces ultrashort pulses (30-100 fs FWHM) with a peak radiation power in the GW level and with full transverse coherence. The wavelength was tuned in the range of 95-105 nm.

Absorption measurements above the K edges of the low-Z atoms, C, N, O, and F, are discussed, which utilize 250-1000-eV synchrotron radiation. The paper emphasizes experimental procedures of soft x-ray absorption and extended absorption fine structure (EXAFS) measurements as well as applications and future prospects of such studies. In particular, we discuss such applications as surface EXAFS, surface absorption fine structure, and ion yield EXAFS measurements.

A technique for the single step separation of human thymus derived (T) and Bursa equivalent (B) lymphocytes was developed. Density separation of B lymphocytes and T lymphocyte-sheep red blood cell (SRBC) rosettes on Ficoll-Hypaque was modified by pretreatment of the SRBC with 2 aminoethylisothiouronium bromide hydrobromide. This modification yielded significantly purer populations of T and B cells. Up to 15 X 10(7) were separated without increasing contamination allowing for the recovery of B lymphocytes as well as T lymphocytes in sufficient numbers to use in functional assays.

Direct iodination of morphine or dihydromorphine with iodine-125 results in products that bind to antibody raised by immunization of animals with a 3-O-carboxymethylmorphine/bovine serum albumin immunogen. Iodination of morphine or dihydromorphine with iodine-127 under identical conditions failed to yield these immunologically active products, suggesting that the results obtained with iodine-125 are in part due to a radiolytic reaction not observed with the iodine-127.