Thin n-in-p planar pixel sensors and active edge sensors for the ATLAS upgrade at HL-LHC

Silicon pixel modules employing n-in-p planar sensors with an active thickness of 200 $\mu$m, produced at CiS, and 100-200 $\mu$m thin active/slim edge sensor devices, produced at VTT in Finland have been interconnected to ATLAS FE-I3 and FE-I4 read-out chips. The thin sensors are designed for high energy physics collider experiments to ensure radiation hardness at high fluences. Moreover, the active edge technology of the VTT production maximizes the sensitive region of the assembly, allowing for a reduced overlap of the modules in the pixel layer close to the beam pipe. The CiS production includes also four chip sensors according to the module geometry planned for the outer layers of the upgraded ATLAS pixel detector to be operated at the HL-LHC. The modules have been characterized using radioactive sources in the laboratory and with high precision measurements at beam tests to investigate the hit efficiency and charge collection properties at different bias voltages and particle incidence angles. The performance of the different sensor thicknesses and edge designs are compared before and after irradiation up to a fluence of $1.4\times10^{16}n_{eq}/cm^{2}$.Comment: In proceedings of the 10th International Conference on Position Sensitive Detectors, PSD10 201

Kultur - Medien - Märkte. Medienentwicklung und kultureller Wandel

Internet, Mobilfunk, interaktives Fernsehen - die Medienwelt verändert sich rasant. In der öffentlichen Wahrnehmung und Diskussion wird hierbei oft primär der Wandel von Übertragungstechniken, von Geschäftsmodellen, von Arbeitsformen und Kommunikationspraxen assoziiert - weniger stark im Zentrum der Aufmerksamkeit stehen jene Veränderungen, die mit Kultur zu tun haben: mit dem Kulturbegriff, der Kulturwirtschaft und dem Kulturbetrieb sowie mit der Kulturpolitik. Diesen vielfach unterbelichteten Feldern widmet sich diese Untersuchung. In den Mittelpunkt der Analyse rücken die Autoren den Wandel der Kulturkonzepte, Trends auf den Medienmärkten und neue Wertschöpfungsketten sowie Produktions-, Vermittlungs- und Rezeptionsformen in ausgewählten Kulturbereichen. Flankiert werden diese mit reichhaltigen empirischen Resultaten versehenen Untersuchungen durch konzeptionelle Reflexionen zum Medienbegriff und zu vergangenen und künftigen Entwicklungen in der Mediennutzung sowie durch forschungsprogrammatische Überlegungen zur weiteren Bearbeitung dieses Feldes. Der Band liefert eine umfassende Übersicht über zentrale Begriffe und relevante Befunde und einen profunden Einblick in die komplexen Wechselwirkungen zwischen Medien und Kultur

Ectopic leptin production by intraocular pancreatic islet organoids ameliorates the metabolic phenotype of ob/ob mice

The pancreatic islets of Langerhans consist of endocrine cells that secrete peptide hormones into the blood circulation in response to metabolic stimuli. When transplanted into the anterior chamber of the eye (ACE), pancreatic islets engraft and maintain morphological features of native islets as well as islet-specific vascularization and innervation patterns. In sufficient amounts, intraocular islets are able to maintain glucose homeostasis in diabetic mice. Islet organoids (pseudo-islets), which are formed by self-reassembly of islet cells following disaggregation and genetic manipulation, behave similarly to native islets. Here, we tested the hypothesis that genetically engineered intraocular islet organoids can serve as production sites for leptin. To test this hypothesis, we chose the leptin-deficient ob/ob mouse as a model system, which becomes severely obese, hyperinsulinemic, hyperglycemic, and insulin resistant. We generated a Tet-OFF-based beta-cell-specific adenoviral expression construct for mouse leptin, which allowed efficient transduction of native beta-cells, optical monitoring of leptin expression by co-expressed fluorescent proteins, and the possibility to switch-off leptin expression by treatment with doxycycline. Intraocular transplantation of islet organoids formed from transduced islet cells, which lack functional leptin receptors, to ob/ob mice allowed optical monitoring of leptin expression and ameliorated their metabolic phenotype by improving bodyweight, glucose tolerance, serum insulin, and C-peptide levels

PI3K-C2 alpha Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation

Insulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question is to mechanistically explain how an insulin target cell/tissue can be insulin resistant in one biological function and insulin sensitive in another at the same time. Here, we provide evidence that in pancreatic beta cells, knockdown of PI3K-C2 alpha expression results in rerouting of the insulin signal from insulin receptor (IR)-B/PI3K-C2 alpha/PKB-mediated metabolic signaling to IR-B/Shc/ERK-mediated mitogenic signaling, which allows the beta cell to switch from a highly glucose-responsive, differentiated state to a proliferative state. Our data suggest the existence of IR-cascade-selective insulin resistance, which allows rerouting of the insulin signal within the same target cell. Hence, factors involved in the rerouting of the insulin signal represent tentative therapeutic targets in the treatment of insulin resistance.11108Ysciescopu

Anomalous infrared spectra of hybridized phonons in type-I clathrate Ba8_8Ga16_{16}Ge30_{30}

The optical conductivity spectra of the rattling phonons in the clathrate Ba$_8$Ga$_{16}$Ge$_{30}$ are investigated in detail by use of the terahertz time-domain spectroscopy. The experiment has revealed that the lowest-lying vibrational mode of a Ba(2)$^{2+}$ ion consists of a sharp Lorentzian peak at 1.2 THz superimposed on a broad tail weighted in the lower frequency regime around 1.0 THz. With decreasing temperature, an unexpected linewidth broadening of the phonon peak is observed, together with monotonic softening of the phonon peak and the enhancement of the tail structure. These observed anomalies are discussed in terms of impurity scattering effects on the hybridized phonon system of rattling and acoustic phonons.Comment: Submitted to JPS

Screening of Human Tumor Antigens for CD4+ T Cell Epitopes by Combination of HLA-Transgenic Mice, Recombinant Adenovirus and Antigen Peptide Libraries

BACKGROUND: As tumor antigen-specific CD4+ T cells can mediate strong therapeutic anti-tumor responses in melanoma patients we set out to establish a comprehensive screening strategy for the identification of tumor-specific CD4+ T cell epitopes suitable for detection, isolation and expansion of tumor-reactive T cells from patients. METHODS AND FINDINGS: To scan the human melanoma differentiation antigens TRP-1 and TRP-2 for HLA-DRB1*0301-restricted CD4+ T cell epitopes we applied the following methodology: Splenocytes of HLA-DRB1*0301-transgenic mice immunized with recombinant adenovirus encoding TRP-1 (Ad5.TRP-1) or TRP-2 (Ad5.TRP-2) were tested for their T cell reactivity against combinatorial TRP-1- and TRP-2-specific peptide libraries. CD4+ T cell epitopes thus identified were validated in the human system by stimulation of peripheral blood mononuclear cells (PBMC) from healthy donors and melanoma patients. Using this strategy we observed that recombinant Ad5 induced strong CD4+ T cell responses against the heterologous tumor antigens. In Ad5.TRP-2-immunized mice CD4+ T cell reactivity was detected against the known HLA-DRB1*0301-restricted TRP-2(60-74) epitope and against the new epitope TRP-2(149-163). Importantly, human T cells specifically recognizing target cells loaded with the TRP-2(149-163)-containing library peptide or infected with Ad5.TRP-2 were obtained from healthy individuals, and short term in vitro stimulation of PBMC revealed the presence of epitope-reactive CD4+ T cells in melanoma patients. Similarly, immunization of mice with Ad5.TRP-1 induced CD4+ T cell responses against TRP-1-derived peptides that turned out to be recognized also by human T cells, resulting in the identification of TRP-1(284-298) as a new HLA-DRB1*0301-restricted CD4+ T cell epitope. CONCLUSIONS: Our screening approach identified new HLA-DRB1*0301-restricted CD4+ T cell epitopes derived from melanoma antigens. This strategy is generally applicable to target antigens of other tumor entities and to different HLA class II molecules even without prior characterization of their peptide binding motives

Magnetotransport near a quantum critical point in a simple metal

We use geometric considerations to study transport properties, such as the conductivity and Hall coefficient, near the onset of a nesting-driven spin density wave in a simple metal. In particular, motivated by recent experiments on vanadium-doped chromium, we study the variation of transport coefficients with the onset of magnetism within a mean-field treatment of a model that contains nearly nested electron and hole Fermi surfaces. We show that most transport coefficients display a leading dependence that is linear in the energy gap. The coefficient of the linear term, though, can be small. In particular, we find that the Hall conductivity $\sigma_{xy}$ is essentially unchanged, due to electron-hole compensation, as the system goes through the quantum critical point. This conclusion extends a similar observation we made earlier for the case of completely flat Fermi surfaces to the immediate vicinity of the quantum critical point where nesting is present but not perfect.Comment: 11 pages revtex, 4 figure

Human islet microtissues as an in vitro and an in vivo model system for diabetes

Loss of pancreatic β-cell function is a critical event in the pathophysiology of type 2 diabetes. However, studies of its underlying mechanisms as well as the discovery of novel targets and therapies have been hindered due to limitations in available experimental models. In this study we exploited the stable viability and function of standardized human islet microtissues to develop a disease-relevant, scalable, and reproducible model of β-cell dysfunction by exposing them to long-term glucotoxicity and glucolipotoxicity. Moreover, by establishing a method for highly-efficient and homogeneous viral transduction, we were able to monitor the loss of functional β-cell mass in vivo by transplanting reporter human islet microtissues into the anterior chamber of the eye of immune-deficient mice exposed to a diabetogenic diet for 12 weeks. This newly developed in vitro model as well as the described in vivo methodology represent a new set of tools that will facilitate the study of β-cell failure in type 2 diabetes and would accelerate the discovery of novel therapeutic agents