Cross-calibration of a combined electrostatic and time-of-flight analyzer for energy- and charge-state-resolved spectrometry of tin laser-produced plasma.

We present the results of the calibration of a channeltron-based electrostatic analyzer operating in time-of-flight mode (ESA-ToF) using tin ions resulting from laser-produced plasma, over a wide range of charge states and energies. Specifically, the channeltron electron multiplier detection efficiency and the spectrometer resolution are calibrated, and count rate effects are characterized. With the obtained overall response function, the ESA-ToF is shown to accurately reproduce charge-integrated measurements separately and simultaneously obtained from a Faraday cup (FC), up to a constant factor the finding of which enables absolute cross-calibration of the ESA-ToF using the FC as an absolute benchmark. Absolute charge-state-resolved ion energy distributions are obtained from ns-pulse Nd:YAG-laser-produced microdroplet tin plasmas in a setting relevant for state-of-the-art extreme ultraviolet nanolithography.

Extreme ultraviolet light from a tin plasma driven by a 2-µm-wavelength laser.

An experimental study of laser-produced plasmas is performed by irradiating a planar tin target by laser pulses, of 4.8 ns duration, produced from a KTP-based 2-µm-wavelength master oscillator power amplifier. Comparative spectroscopic investigations are performed for plasmas driven by 1-µm- and 2-µm-wavelength pulsed lasers, over a wide range of laser intensities spanning 0.5 - 5 × 1011 W/cm 2. Similar extreme ultraviolet (EUV) spectra in the 5.5-25.5 nm wavelength range and underlying plasma ionicities are obtained when the intensity ratio is kept fixed at I1µm/I2µm = 2.4(7). Crucially, the conversion efficiency (CE) of 2-µm-laser energy into radiation within a 2% bandwidth centered at 13.5 nm relevant for industrial applications is found to be a factor of two larger, at a 60 degree observation angle, than in the case of the denser 1-µm-laser-driven plasma. Our findings regarding the scaling of the optimum laser intensity for efficient EUV generation and CE with drive laser wavelength are extended to other laser wavelengths using available literature data.

The LVV Auger line shape of sulfur on copper studied by Auger photoelectron coincidence spectroscopy.

We have studied the line shapes of Cu(0 0 1)-p (2 × 2)S L2VV and L3VV Auger decay by means of Auger photoelectron coincidence spectroscopy. Measuring the LVV Auger spectrum in coincidence with S 2p1/2 and 2p3/2 photoelectrons respectively, we have been able to separate the two overlapping Auger spectra and determine their intrinsic line shapes. The two Auger transitions, though shifted in energy, display an identical line shape whose main features can be qualitatively understood considering a single particle approximation but are better described within a Cini-Sawatzky (CS) approach. Comparison between the experimental and the CS calculated spectra confirms that a substantial part of the Auger lines (∼20%) can be ascribed to decay events accompanied by the excitation of one additional electron-hole pair in the valence band. For the first time, the locality of the Auger process combined with the surface sensitivity of the APECS technique and its ability to separate overlapping structures are used to study Auger transitions taking place at the the surface states of a S/noble-metal interface.

Dynamic screening probed by core-resonant double photoemission from surfaces.

The universal response of a sudden created core hole, predicted to occur on an attosecond (10(-18) s) time scale, lacks an experimental demonstration. With a two-dimensional coincidence spectrometer, we demonstrate an extensive energy sharing between the Ag 4p photoelectron and the N2,3VV Auger electron exceeding 10 eV. This energy width provides access to the time scale of the emission process. This is the fingerprint of the dynamic fluctuation process 4p(-1)⇌4d(-2)4f. The shakeup induced interband transitions from the Ag(100) surface are also identified by comparing the coincidence spectrum with the M4,5VV Auger transitions.

Exploring highly correlated materials via electron pair emission: the case of NiO/Ag(100).

Metal oxides like NiO are usually termed 'highly correlated', because the material properties are decisively determined by the electron-electron interaction. This makes them interesting candidates for electron pair spectroscopy which is particularly sensitive to the electron correlation. We have prepared ultrathin NiO/Ag(100) films and studied the electron pair emission upon electron impact. Compared to the metal substrate we observe an increase of the coincidence intensity by a factor of 8 for NiO. Thickness dependent measurements prove that this enhancement is an intrinsic effect rather than due to a mean free path increase of the oxide. The Néel temperature T(N) of NiO films displays a thickness dependence which allows us to tune T(N). We performed temperature dependent measurements and observed no temperature dependence of the coincidence spectra. This proves that the electron pair emission probes the local correlation rather than long range order. An enhanced coincidence intensity was also found for other oxide phases compared to their corresponding metal phases.

Tumor necrosis factor alpha and CD40 ligand antagonize the inhibitory effects of interleukin 10 on T-cell stimulatory capacity of dendritic cells.

Interleukin (IL)-10 secretion by tumor cells was demonstrated to be one of the mechanisms by which tumor cells can escape immunological recognition and destruction. In dendritic cells (DCs), which are currently used for vaccination therapies for malignant diseases, IL-10 inhibits IL-12 production and induces a state of antigen-specific anergy in CD4- and CD8-positive T cells. We therefore analyzed the effects of different activation stimuli including lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, and CD40 ligation on IL-10 mediated inhibition of DC development and stimulatory capacity. In our study, the addition of IL-10 to the cultures containing granulocyte/macrophage-colony stimulating factor and IL-4 with or without LPS completely inhibited the generation of DCs from peripheral blood monocytes. These cells remained CD14 positive and expressed high levels of IL-10 receptor (IL-10R), suggesting that IL-10 mediates its effects by up-regulating the IL-10R. In contrast, the simultaneous incubation of monocytes with IL-10 and TNF-alpha or soluble CD40 ligand (sCD40L) resulted in the generation of CD83-positive DCs, induction of nuclear localized RelB, and inhibition of IL-10R up-regulation. DCs grown in the presence of IL-10 and TNF-alpha or sCD40L elicited efficient CTL responses against viral and tumor-associated peptide antigens, which, however, were reduced as compared with DC cultures generated without IL-10. IL-10 decreased the production of IL-6 and the expression of IL-12 in the presence of TNF-alpha or sCD40L, but it had no effect on IL-15, IL-18, and TNF-alpha secretion. Our results show that TNF-alpha or CD40 ligation can antagonize the IL-10-mediated inhibition on DC function, suggesting that depending on activation stimuli, the presence of IL-10 does not necessarily result in T-cell anergy.

Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies.

The tumor-associated antigen MUC1 is overexpressed on various hematological and epithelial malignancies and is therefore a suitable candidate for broadly applicable vaccine therapies. It was demonstrated that major histocompatibility complex (MHC)-unrestricted cytotoxic T cells can recognize epitopes of the MUC1 protein core localized in the tandem repeat domain. There is increasing evidence now that MHC-restricted T cells can also be induced after immunization with the MUC1 protein or segments of the core tandem repeat. Using a computer analysis of the MUC1 amino acid sequence, we identified two novel peptides with a high binding probability to the HLA-A2 molecule. One of the peptides is derived from the tandem repeat region and the other is derived from the leader sequence of the MUC1 protein, suggesting that, in contrast to previous reports, the MUC1-directed immune responses are not limited to the extracellular tandem repeat domain. Cytotoxic T cells (CTL) were generated from several healthy donors by primary in vitro immunization using peptide-pulsed dendritic cells. The addition of a Pan-HLA-DR binding peptide PADRE as a T-helper epitope during the in vitro priming resulted in an increased cytotoxic activity of the MUC1-specific CTL and a higher production of cytokines such as interleukin-12 and interferon-gamma in the cell cultures, demonstrating the importance of CD4 cells for an efficient CTL priming. The peptide induced CTL lysed tumors endogenously expressing MUC1 in an antigen-specific and HLA-A2-restricted fashion, including breast and pancreatic tumor cells as well as renal cell carcinoma cells, showing that these peptides are shared among many tumors. The use of MUC1-derived peptides could provide a broadly applicable approach for the development of dendritic cell-based vaccination therapies.

Managed care organizations and products.

Managed care organizations and their products will continue to change in response to consumer demands, competitive pressures, and regulatory requirements. Providers who gain an understanding of the world managed care organizations live in can also expect to influence these organizations for mutual benefit. Just as managed care organizations differ in the sophistication of their functional elements, providers and their organizations differ in their ability to shift their focus from the physician-patient relationship to improving the health of a population. As the future of managed care evolves, there are opportunities for those physicians who strive for a greater understanding of the broad spectrum of forces shaping the health care industry.