The underdoped-overdoped transition in YBa_2Cu_3O_x

Oxygen doping in metallic YBa_2Cu_3O_x induces quadrupolar "alpha-ortho'', and breathing "beta-ortho" deformations of the CuO_2 planes. Breathing beta-ortho deformations favour hybridizations of the pd sigma Cu3d_x^2-y^2 - O2p_x,y with the pd pi Cu3d_x,z, 3d_y,z-O2p_z bands relaxing the confinement of the carriers in the overdoped regime, x>6.95.Comment: 2 pages (LaTex2e), 1 eps figure. Submitted to Physica

T-cell clonotypes in cancer

Cells of the immune system spontaneously recognize autologous tumor cells and T cells are believed to be the main effector cells for the immune surveillance of cancer. Recent advances in our understanding of basic and tumor immunology together with methodological developments implies that tumor specific T cells can now be studied functionally, phenotypically as well as molecularly. T cells recognize peptide antigens in the context of MHC molecules through the clonally distributed T-cell receptor (TCR), thus, the clonal distribution of the TCR offers the means to detect and track specific T cells based upon detection of the unique TCR. In this review, we present and discuss available data on TCR utilization of tumor specific T cells in murine models as well as spontaneous and treatment induced anti-tumor T-cell responses in humans

Bootstrap reservoir concepts for electro-hydraulic compact cylinder drives

This paper presents a conceptual study aiming to improve the compactness of electro-hydraulic compact drives (ECD ). In most current ECD architectures, gas accumulators are used as volume compensators for the flow imbalance emerging whenever asymmetric single rod cylinders are used. To stay within a required reservoir pressure range typically from two to four bar, a large gas volume is required, compromising system compactness. Combining conventional ECD architectures with a bootstrap reservoir offers a greater degree of freedom in system design, which enables downsizing or avoidance of the gas volume. Another potential benefit by including a bootstrap reservoir is the possibility of elevating the backpressure of the ECD thus enhancing drive stiffness, expanding the application range and market acceptance. Based on an open analysis of the solution space occurring when introducing a bootstrap reservoir, three system architectures are selected for a conceptual study. The results show that the downsizing potential is strongly dependent on the maximum friction force and the area ratio of the bootstrap reservoir pistons, while a linear analysis reveals that for some system architectures the bootstrap reservoir may severely influence the system dynamics. Simulation results confirm the functionality of the proposed system architectures, and show that a potential for downsizing/avoiding the gas volume, as well as increasing the ECD stiffness is present

The Melanoma Inhibitor of Apoptosis Protein: A Target for Spontaneous Cytotoxic T Cell Responses

The identification of tumor antigens which expression is essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. The melanoma inhibitor of apoptosis protein, ML-IAP (also named livin) counteracts apoptosis induced by death receptors, hypooxgenic conditions, or chemotherapeutic agents. Thus, elevated expression of ML-IAP renders melanoma cells resistant to apoptotic stimuli and thereby potentially contributes to the oncogenic phenotype. Here, we demonstrate that T cells in a large proportion of melanoma patients infiltrating the tumor or circulating in the peripheral blood specifically recognize ML-IAP-derived peptides. Interestingly, the responses against the peptide epitope ML-IAP280–289 were not restricted to melanoma patients but present among peripheral blood T cells in a few healthy controls. In situ peptide/HLA-A2 multimer staining, however, confirmed the infiltration of ML-IAP-reactive cells into the tumor microenvironment. Moreover, ML-IAP-reactive T cells isolated by magnetic beads coated with peptide/HLA-A2 complexes were cytotoxic against HLA-matched melanoma cells. In conclusion, out data strongly indicate ML-IAP as a suitable target for immunologic intervention

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer

Immunological Memory Transferred with CD4 T Cells Specific for Tuberculosis Antigens Ag85B-TB10.4: Persisting Antigen Enhances Protection

BACKGROUND:High levels of death and morbidity worldwide caused by tuberculosis has stimulated efforts to develop a new vaccine to replace BCG. A number of Mycobacterium tuberculosis (Mtb)-specific antigens have been synthesised as recombinant subunit vaccines for clinical evaluation. Recently a fusion protein of TB antigen Ag85B combined with a second immunodominant TB antigen TB10.4 was emulsified with a novel non-phospholipid-based liposomal adjuvant to produce a new subunit vaccine, investigated here. Currently, there is no consensus as to whether or not long-term T cell memory depends on a source of persisting antigen. To explore this and questions regarding lifespan, phenotype and cytokine patterns of CD4 memory T cells, we developed an animal model in which vaccine-induced CD4 memory T cells could transfer immunity to irradiated recipients. METHODOLOGY/PRINCIPAL FINDINGS:The transfer of protective immunity using Ag85B-TB10.4-specific, CD45RB(low) CD62L(low) CD4 T cells was assessed in sub-lethally irradiated recipients following challenge with live BCG, used here as a surrogate for virulent Mtb. Donor T cells also carried an allotype marker allowing us to monitor numbers of antigen-specific, cytokine-producing CD4 T cells in recipients. The results showed that both Ag85B-TB10.4 and BCG vaccination induced immunity that could be transferred with a single injection of 3x10(6) CD4 T cells. Ten times fewer numbers of CD4 T cells (0.3x10(6)) from donors immunised with Ag85B-TB10.4 vaccine alone, transferred equivalent protection. CD4 T cells from donors primed by BCG and boosted with the vaccine similarly transferred protective immunity. When BCG challenge was delayed for 1 or 2 months after transfer (a test of memory T cell survival) recipients remained protected. Importantly, recipients that contained persisting antigen, either live BCG or inert vaccine, showed significantly higher levels of protection (p<0.01). Overall the numbers of IFN-gamma-producing CD4 T cells were poorly correlated with levels of protection. CONCLUSIONS/SIGNIFICANCE:The Ag85B-TB10.4 vaccine, with or without BCG-priming, generated TB-specific CD4 T cells that transferred protective immunity in mice challenged with BCG. The level of protection was enhanced in recipients containing a residual source of specific antigen that could be either viable or inert

Thermo-Hydraulic Modelling and Experimental Validation of an Electro-Hydraulic Compact Drive

Electro-hydraulic compact drives (ECDs) are an emerging technology for linear actuation in a wide range of applications. Especially within the low power range of 5–10 kW, the plug-and-play capability, good energy efficiency and small space requirements of ECDs render this technology a promising alternative to replace conventional valve-controlled linear drive solutions. In this power range, ECDs generally rely on passive cooling to keep oil and system temperatures within the tolerated range. When expanding the application range to larger power classes, passive cooling may not be sufficient. Research investigating the thermal behaviour of ECDs is limited but indeed required for a successful expansion of the application range. In order to obtain valuable insights into the thermal behaviour of ECDs, thermo-hydraulic simulation is an important tool. This may enable system design engineers to simulate thermal behaviour and thus develop proper thermal designs during the early design phase, especially if such models contain few parameters that can be determined with limited information available. Our paper presents a lumped thermo-hydraulic model derived from the conservation of mass and energy. The derived model was experimentally validated based on experimental data from an ECD prototype. Results show good accuracy between measured and simulated temperatures. Even a simple thermal model containing only a few thermal resistances may be sufficient to predict steady-state and transient temperatures with reasonable accuracy. The presented model may be used for further investigations into the thermal behaviour of ECDs and thus toward proper thermal designs required to expand the application range.publishedVersio

Dust properties inside molecular clouds from coreshine modeling and observations

Context. Using observations to deduce dust properties, grain size distribution, and physical conditions in molecular clouds is a highly degenerate problem. Aims. The coreshine phenomenon, a scattering process at 3.6 and 4.5 $\mu$m that dominates absorption, has revealed its ability to explore the densest parts of clouds. We want to use this effect to constrain the dust parameters. The goal is to investigate to what extent grain growth (at constant dust mass) inside molecular clouds is able to explain the coreshine observations. We aim to find dust models that can explain a sample of Spitzer coreshine data. We also look at the consistency with near-infrared data we obtained for a few clouds. Methods. We selected four regions with a very high occurrence of coreshine cases: Taurus-Perseus, Cepheus, Chameleon and L183/L134. We built a grid of dust models and investigated the key parameters to reproduce the general trend of surface bright- nesses and intensity ratios of both coreshine and near-infrared observations with the help of a 3D Monte-Carlo radiative transfer code. The grid parameters allow to investigate the effect of coagulation upon spherical grains up to 5 $\mu$m in size derived from the DustEm diffuse interstellar medium grains. Fluffiness (porosity or fractal degree), ices, and a handful of classical grain size distributions were also tested. We used the near- and mostly mid-infrared intensity ratios as strong discriminants between dust models. Results. The determination of the background field intensity at each wavelength is a key issue. In particular, an especially strong background field explains why we do not see coreshine in the Galactic plane at 3.6 and 4.5 $\mu$m. For starless cores, where detected, the observed 4.5 $\mu$m / 3.6 $\mu$m coreshine intensity ratio is always lower than $\sim$0.5 which is also what we find in the models for the Taurus-Perseus and L183 directions. Embedded sources can lead to higher fluxes (up to four times greater than the strongest starless core fluxes) and higher coreshine ratios (from 0.5 to 1.1 in our selected sample). Normal interstellar radiation field conditions are sufficient to find suitable grain models at all wavelengths for starless cores. The standard interstellar grains are not able to reproduce observations and, due to the multi-wavelength approach, only a few grain types meet the criteria set by the data. Porosity does not affect the flux ratios while the fractal dimension helps to explain coreshine ratios but does not seem able to reproduce near-infrared observations without a mix of other grain types. Conclusions. Combined near- and mid-infrared wavelengths confirm the potential to reveal the nature and size distribution of dust grains. Careful assessment of the environmental parameters (interstellar and background fields, embedded or nearby reddened sources) is required to validate this new diagnostic