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Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4+ and CD8+ T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0–84 mo) and the median OS was 48 mo (range, 3–106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16–29 mo), and median OS was 48 mo (CI, not estimable). CD8+ T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.

NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a range of different tumor types. Each construct was first tested individually at two different dose levels and then in a prime-boost setting with recombinant vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were well tolerated either individually or together. NY-ESO-1-specific antibody responses and/or specific CD8 and CD4 T cell responses directed against a broad range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations at monthly intervals in a high proportion of patients. CD8 T cell clones derived from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma target cells. In several patients with melanoma, there was a strong impression that the natural course of the disease was favorably influenced by vaccination.

Cancer-testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40-50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody positive at the outset of the study. Primary peptide-specific CD8+ T-cell reactions and delayed-type hypersensitivity responses were generated in four of seven NY-ESO-1 antibody-negative patients. Induction of a specific CD8+ T-cell response to NY-ESO-1 in immunized antibody-negative patients was associated with disease stabilization and objective regression of single metastases. NY-ESO-1 antibody-positive patients did not develop significant changes in baseline NY-ESO-1-specific T-cell reactivity. However, stabilization of disease and regression of individual metastases were observed in three of five immunized patients. These results demonstrate that primary NY-ESO-1-specific CD8+ T-cell responses can be induced by intradermal immunization with NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the potential to alter the natural course of NY-ESO-1-expressing tumors.

According to classic text books on lichen biology, the phenolic secondary chemicals in lichens have antibiotic effects on soil microorganisms and mycorrhizal fungi in ecosystems. However, the experimental evidence for this under natural conditions is still relatively scarce. We examined some of the assumptions behind the concept of antimicrobial effects of lichen secondary substances: (1) the secondary substances of Cladonia stellaris, usnic and perlatolic acids, are leached out from the lichens by rainwater; (2) these substances inhibit the microbial activity of soil, and; (3) since they are extremely resistant to microbial decomposition, the soil underneath a continuous lichen mat is enriched in usnic and perlatolic acids. Our results did not support any of these assumptions. The evidence for the antimicrobial activity of lichen secondary substances seems to be weak in comparison to other suggested functions such as light filtering and herbivore protection. We suggest that it is time to re-evaluate the evidence for the antimicrobial ecological role of lichen secondary substances in natural systems.

This collection brings together distinguished international authors, who pay tribute to von Hirsch by engaging with topics on which he himself has focussed. Together, they articulate and defend the ideal of a liberal criminal justice system.

We analyze the transfer function of a three-dimensional atomic Bragg beamsplitter formed by two counterpropagating pulsed Gaussian laser beams. Even for ultracold atomic ensembles, the transfer efficiency depends significantly on the residual velocity of the particles as well as on losses into higher diffraction orders. Additional aberrations are caused by the spatial intensity variation and wavefront curvature of the Gaussian beam envelope, studied with (3+1)D numerical simulations. The temporal pulse shape also affects the transfer efficiency significantly. Thus, we consider the practically important rectangular-, Gaussian-, Blackman- and hyperbolic secant pulses. For the latter, we can describe the time-dependent response analytically with the Demkov-Kunike method. The experimentally observed stretching of the \\(\\pi\\)-pulse time is explained from a renormalization of the simple Pendell\"osung frequency. Finally, we compare the analytical predictions for the velocity-dependent transfer function with effective (1+1)D numerical simulations for pulsed Gaussian beams, as well as experimental data and find very good agreement, considering a mixture of Bose-Einstein condensate and thermal cloud.

The number of activities in Antarctica is growing continuously. At the same time their diversity is increasing as well. Beside classical types such as scientific research, related logistic activities, tourism and fishing, we can also find new types of commercial and non-commercial non-governmental activities in Antarctica today. Although these activities do not play such an important role in respect to activities in Antarctica as a whole, they are often difficult to manage, especially from the point of view of a competent authority which has to decide whether or not such an activity may proceed in Antarctica. Why might it be difficult for Parties to regulate such activities under their domestic law? The following text illustrates some of these difficulties. It begins by describing the international legal background for the assessment of Antarctic activities. Following this, a recent example of an intended art project organised in Germany will be given, raising several important questions on the adequacy of the existing legal provisions. Finally the handling of this case under German implementing legislation will be outlined.

New challenges posing new management problems in the context of the permanent installation of a bronze sculpture, were presented. Antarctic Treaty Parties would have to tackle these problems and recognize that there were possible gaps or at least inadequate regulations in the existing Antarctic Treaty System in respect of these new forms of activities, especially since they were not considered when the Environmental Protocol was negotiated at the end of the 1980s and early 1990s. At the XXVIII Antarctic Treaty Consultative Meeting in Stockholm in 2005, Antarctic Treaty Parties started land based tourism facilities with the principles of the Antarctic Treaty and the Environmental Protocol. And although it did not raise the exact questions arising from the example - because of its focus on permanent infrastructure for tourism purposes - it provided important contributions on the problems Parties might have in dealing with 'new' types of activities.

The velocity distribution of a hot ionic beam can be filtered with a narrow stimulated Raman process to prepare a colder subensemble, as substantiated in this theoretical analysis. Using two counter-propagating, far-detuned lasers, we can define a \\(\\pi\\)-pulse for the resonant velocity to transfer atoms within the linewidth of the Raman resonance between the ground-states of a \\(\\Lambda\\)-system. Spontaneous emission from the two single-photon resonances, as well as the ground-state decoherence induced by laser noise, diminishes the efficiency of the filter. From a comprehensive master equation, we obtain conditions for the optimal frequency pair of the lasers and evaluate the filter performance numerically, as well as analytically. If we apply this analysis to current \\(^{40}\\)Ca\\(^+\\) ion experiments, we obtain a sensitivity for measuring high ion acceleration voltages on the ppm level or below.

NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a range of different tumor types. Each construct was first tested individually at two different dose levels and then in a prime-boost setting with recombinant vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were well tolerated either individually or together. NY-ESO-1-specific antibody responses and/or specific CD8 and CD4 T cell responses directed against a broad range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations at monthly intervals in a high proportion of patients. CD8 T cell clones derived from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma target cells. In several patients with melanoma, there was a strong impression that the natural course of the disease was favorably influenced by vaccination.