A multi-purpose modular system for high-resolution microscopy at high hydrostatic pressure

We have developed a modular system for high-resolution microscopy at high hydrostatic pressure. The system consists of a pressurised cell of volume ~100 microlitres, a temperature controlled holder, a ram and a piston. We have made each of these components in several versions which can be interchanged to allow a wide range of applications. Here, we report two pressure cells with pressure ranges 0.1-700MPa and 0.1-100MPa, which can be combined with hollow or solid rams and pistons. Our system is designed to work with fluorescent samples (using a confocal or epifluorescence microscope), but also allows for transmitted light microscopy via the hollow ram and piston. The system allows precise control of pressure and temperature [-20-70C], as well as rapid pressure quenching. We demonstrate its performance and versatility with two applications: time-resolved imaging of colloidal phase transitions caused by pressure changes between 0.1MPa and 101MPa, and imaging the growth of Escherichia coli bacteria at 50MPa. We also show that the isotropic-nematic phase transition of pentyl-cyanobiphenyl (5CB) liquid crystal provides a simple, convenient and accurate method for calibrating pressure in the range 0.1-200MPa

How geography matters: neglected dimensions in contemporary migration research

In Asia, migration is a complex phenomenon, the same as worldwide. The approaches of diaspora as well as transnational migration and transnational social spaces describe contemporary migration processes and are at the centre of this paper. Our major critique about these approaches is their dominantly socio-cultural perspective on migration, the missing link to other existing social theory, and missing consideration of the importance of place and identity, and the multiple ways how people perceive and construct space. To address this critique we present innovative geographical research showing the potential of social geography to contribute to the understanding of increasing mobility worldwide

Goal-conflict detection based on temporal satisfiability checking

Goal-oriented requirements engineering approaches propose capturing how a system should behave through the speci ca- tion of high-level goals, from which requirements can then be systematically derived. Goals may however admit subtle situations that make them diverge, i.e., not be satis able as a whole under speci c circumstances feasible within the domain, called boundary conditions . While previous work al- lows one to identify boundary conditions for con icting goals written in LTL, it does so through a pattern-based approach, that supports a limited set of patterns, and only produces pre-determined formulations of boundary conditions. We present a novel automated approach to compute bound- ary conditions for general classes of con icting goals expressed in LTL, using a tableaux-based LTL satis ability procedure. A tableau for an LTL formula is a nite representation of all its satisfying models, which we process to produce boundary conditions that violate the formula, indicating divergence situations. We show that our technique can automatically produce boundary conditions that are more general than those obtainable through existing previous pattern-based approaches, and can also generate boundary conditions for goals that are not captured by these patterns

Alternative axiomatics and complexity of deliberative STIT theories

We propose two alternatives to Xu's axiomatization of the Chellas STIT. The first one also provides an alternative axiomatization of the deliberative STIT. The second one starts from the idea that the historic necessity operator can be defined as an abbreviation of operators of agency, and can thus be eliminated from the logic of the Chellas STIT. The second axiomatization also allows us to establish that the problem of deciding the satisfiability of a STIT formula without temporal operators is NP-complete in the single-agent case, and is NEXPTIME-complete in the multiagent case, both for the deliberative and the Chellas' STIT.Comment: Submitted to the Journal of Philosophical Logic; 13 pages excluding anne

Colloid-stabilized emulsions: behaviour as the interfacial tension is reduced

We present confocal microscopy studies of novel particle-stabilized emulsions. The novelty arises because the immiscible fluids have an accessible upper critical solution temperature. The emulsions have been created by beginning with particles dispersed in the single-fluid phase. On cooling, regions of the minority phase nucleate. While coarsening these nuclei become coated with particles due to the associated reduction in interfacial energy. The resulting emulsion is arrested, and the particle-coated interfaces have intriguing properties. Having made use of the binary-fluid phase diagram to create the emulsion we then make use of it to study the properties of the interfaces. As the emulsion is re-heated toward the single-fluid phase the interfacial tension falls and the volume of the dispersed phase drops. Crumpling, fracture or coalescence can follow. The results show that the elasticity of the interfaces has a controlling influence over the emulsion behaviour.Comment: Submitted for the proceedings of the 6th Liquid Matter Conference, held in Utrecht (NL) in July 200

Single-photon-emitting optical centers in diamond fabricated upon Sn implantation

The fabrication of luminescent defects in single-crystal diamond upon Sn implantation and annealing is reported. The relevant spectral features of the optical centers (emission peaks at 593.5 nm, 620.3 nm, 630.7 nm and 646.7 nm) are attributed to Sn-related defects through the correlation of their photoluminescence (PL) intensity with the implantation fluence. Single Sn-related defects were identified and characterized through the acquisition of their second-order auto-correlation emission functions, by means of Hanbury-Brown-Twiss interferometry. The investigation of their single-photon emission regime as a function of excitation laser power revealed that Sn-related defects are based on three-level systems with a 6 ns radiative decay lifetime. In a fraction of the studied centers, the observation of a blinking PL emission is indicative of the existence of a dark state. Furthermore, absorption dependence from the polarization of the excitation radiation with about 45 percent contrast was measured. This work shed light on the existence of a new optical center associated with a group-IV impurity in diamond, with similar photo-physical properties to the already well-known Si-V and Ge-V emitters, thus providing results of interest from both the fundamental and applicative points of view.Comment: 10 pages, 4 figure

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

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