TfAP-2 is required for night sleep in Drosophila.

BACKGROUND: The AP-2 transcription factor APTF-1 is crucially required for developmentally controlled sleep behavior in Caenorhabditis elegans larvae. Its human ortholog, TFAP-2beta, causes Char disease and has also been linked to sleep disorders. These data suggest that AP-2 transcription factors may be highly conserved regulators of various types of sleep behavior. Here, we tested the idea that AP-2 controls adult sleep in Drosophila. RESULTS: Drosophila has one AP-2 ortholog called TfAP-2, which is essential for viability. To investigate its potential role in sleep behavior and neural development, we specifically downregulated TfAP-2 in the nervous system. We found that neuronal TfAP-2 knockdown almost completely abolished night sleep but did not affect day sleep. TfAP-2 insufficiency affected nervous system development. Conditional TfAP-2 knockdown in the adult also produced a modest sleep phenotype, suggesting that TfAP-2 acts both in larval as well as in differentiated neurons. CONCLUSIONS: Thus, our results show that AP-2 transcription factors are highly conserved regulators of development and sleep

Hepatoprotective Effects of Milk Thistle (Silybum marianum) Seed Cakes during the Chicken Broiler Fattening

The objective of this work was to verify the hepatoprotective effects of Silybum marianum seed cakes in feed mixtures used for the fattening of chicken broilers to heavier weights. Part of the experiment was to verify the preventive effect of such modified feed mixtures with the use of chlortetracycline medication. The experiment was carried out on 180 ROSS 308 broiler chickens. The chickens were fed complete feed mixtures containing 0.0% (K), 0.2% (P1 and 1.0% (P2) of Silybum marianum seed cakes. The cakes used contained 2.95% of silymarin. On the 44th day of fattening half of the chickens from every group were supplied with chlortetracycline medicated water at a dose of 2 g kg1 live weight. The selected biochemical indices were observed: cholesterol (Chol), glutamyl transferase (GMT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). On the 52nd day of the test, six chickens from each group were euthanized and their liver was taken for histological examination. Adding Silybum marianum seed cakes resulted in a non-significant decrease in the chickens' live weight and in the feed conversion in both experimental groups compared to the control group. The cholesterol levels were highly significantly lower (p p p p p p p < 0.01) the content of lipids and increased the content of glycogen in the liver of both experimental groups

The classification of irreducible admissible mod p representations of a p-adic GL_n

Let F be a finite extension of Q_p. Using the mod p Satake transform, we define what it means for an irreducible admissible smooth representation of an F-split p-adic reductive group over \bar F_p to be supersingular. We then give the classification of irreducible admissible smooth GL_n(F)-representations over \bar F_p in terms of supersingular representations. As a consequence we deduce that supersingular is the same as supercuspidal. These results generalise the work of Barthel-Livne for n = 2. For general split reductive groups we obtain similar results under stronger hypotheses.Comment: 55 pages, to appear in Inventiones Mathematica

Optical properties of an ensemble of G-centers in silicon

We addressed the carrier dynamics in so-called G-centers in silicon (consisting of substitutional-interstitial carbon pairs interacting with interstitial silicons) obtained via ion implantation into a silicon-on-insulator wafer. For this point defect in silicon emitting in the telecommunication wavelength range, we unravel the recombination dynamics by time-resolved photoluminescence spectroscopy. More specifically, we performed detailed photoluminescence experiments as a function of excitation energy, incident power, irradiation fluence and temperature in order to study the impact of radiative and non-radiative recombination channels on the spectrum, yield and lifetime of G-centers. The sharp line emitting at 969 meV ($\sim$1280 nm) and the broad asymmetric sideband developing at lower energy share the same recombination dynamics as shown by time-resolved experiments performed selectively on each spectral component. This feature accounts for the common origin of the two emission bands which are unambiguously attributed to the zero-phonon line and to the corresponding phonon sideband. In the framework of the Huang-Rhys theory with non-perturbative calculations, we reach an estimation of 1.6$\pm$0.1 \angstrom for the spatial extension of the electronic wave function in the G-center. The radiative recombination time measured at low temperature lies in the 6 ns-range. The estimation of both radiative and non-radiative recombination rates as a function of temperature further demonstrate a constant radiative lifetime. Finally, although G-centers are shallow levels in silicon, we find a value of the Debye-Waller factor comparable to deep levels in wide-bandgap materials. Our results point out the potential of G-centers as a solid-state light source to be integrated into opto-electronic devices within a common silicon platform

The Mechanical Behaviour of Ultra Fine Grained Titanium Alloys at High Strain Rates

Within this study the mechanical behaviour of ultra-fine grained Ti-6-22-22S titanium alloy was investigated and compared to coarse grained material. By severe plastic deformation using the cyclic channel die compression process, grain sizes between 300 and 500 nm were obtained. The mechanical behaviour was studied over a wide range of strain rates from 10^(-3) - 107 s^(-1) under compressive loading using different experimental techniques. A significant increase of flow stress with decreasing grain size compared to the coarse grain state was found. An evaluation of the strain hardening behaviour of the UFG material shows a significant increase of the strain hardening coefficient at high strain rates for low plastic deformation. The strain rate sensitivity of the material is found to be constant within a range of strain rates from 10^(-3) to 106 s^(-1) but increases at higher plastic strains. However, compressive deformability is nearly constant up to 102 s-1 and decreased disproportionately at higher rates of strain. With decreasing grain size a significant decrease of compressive deformability was found. The strength at failure is increased with increasing strain rate

Modelling of the Mechanical Behaviour of Ultra-Fine Grained Titanium Alloys at High Strain Rates

Results of numerical simulations of the mechanical behaviour of coarse grained and UFG titanium alloys under quasi-static uniaxial compression and plane shock wave loading are presented in this paper. Constitutive equations predict the strain hardening behaviour, the strain rate sensitivity of the flow stress and the temperature softening of titanium alloys with a range of grain sizes from 20 µm to 100 nm. Characteristics of the mechanical behaviour of UFG a and a+ß titanium alloys in wide range of strain rates are discussed

2OACTIVATION OF T CELLS UPON TREATMENT WITH BISPECIFIC ANTIBODIES CORRELATES WITH THE EXPRESSION OF CO-INHIBITORY RECEPTORS ON TUMOR-INFILTRATING LYMPHOCYTES IN HUMAN LUNG CANCER

Introduction: T cell bispecific antibodies (TCB) are designed to recruit and simultaneously activate T cells against target cells such as tumor cells expressing a particular surface antigen. However, it is currently unknown how immuno-modulatory mechanisms active in the tumor microenvironment such as the expression of T cell co-inhibitory receptors may influence the therapeutic effect of TCBs. Methods: We performed a comprehensive phenotypic analysis of tumor infiltrating immune cells from lung carcinoma digests by multicolour flow cytometry. In particular, expression of T cell co-inhibitory and -stimulatory receptors was analyzed. Tumor digests were treated with catumaxomab, a TCB directed against CD3 and EpCAM. T cell activation and effector functions were assessed upon exposure to catumaxomab. Results: CD8+ T cells in lung carcinoma showed a broad heterogeneity in expression of the T cell co-inhibitory receptors PD-1, Tim-3, CTLA-4, Lag-3 and BTLA. Tumor stage and nodal status correlated with number and intensity of expressed receptors. Upon exposure to catumaxomab, a considerable heterogeneity in T cell activation among different tumors was observed. Of note, T cells expressing high levels and multiple co-inhibitory receptors were more impaired in their activation and effector functions after treatment with catumaxomab indicating a higher level of exhaustion. In a further analysis of CD8+ TIL subsets we found that BTLA+ T cells expressed more additional inhibitory receptors than all other subsets, namely PD-1, Tim-3, CTLA-4 and Lag-3, whereas only a small part of PD-1+ T cells expressed another receptor. Tim-3+ T cells usually co-expressed PD-1, but multiple receptors were found only on a low number of cells. Conclusion: In summary, our data suggest that the activity of TCBs is largely affected by the expression of T cell co-inhibitory receptors on tumor-infiltrating immune cells. Furthermore, these data provide a clinical rationale for combining bispecific antibodies with compounds which antagonize T cell exhaustion. Disclosure: D. Thommen, J. Schreiner, P. Herzig, P. Mueller and A. Zippelius: received research funding from Roche Glycart; V. Karanikas: is employed by Roche Glycart. All other authors have declared no conflicts of interes

ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures

ArachnoServer (www.arachnoserver.org) is a manually curated database providing information on the sequence, structure and biological activity of protein toxins from spider venoms. These proteins are of interest to a wide range of biologists due to their diverse applications in medicine, neuroscience, pharmacology, drug discovery and agriculture. ArachnoServer currently manages 1078 protein sequences, 759 nucleic acid sequences and 56 protein structures. Key features of ArachnoServer include a molecular target ontology designed specifically for venom toxins, current and historic taxonomic information and a powerful advanced search interface. The following significant improvements have been implemented in version 2.0: (i) the average and monoisotopic molecular masses of both the reduced and oxidized form of each mature toxin are provided; (ii) the advanced search feature now enables searches on the basis of toxin mass, external database accession numbers and publication date in ArachnoServer; (iii) toxins can now be browsed on the basis of their phyletic specificity; (iv) rapid BLAST searches based on the mature toxin sequence can be performed directly from the toxin card; (v) private silos can be requested from research groups engaged in venoms-based research, enabling them to easily manage and securely store data during the process of toxin discovery; and (vi) a detailed user manual is now available

Detection of protein aggregation with a Bloch surface wave based sensor

We present the innovative application of a Bloch surface wave based sensor to the detection of protein aggregation. In Hen Egg White Lysozyme (HEWL) solutions, aggregates are discriminated from the monomeric forms in a label-free detection scheme