Walking in the Limits

Walking in the limits is a homogenic artistic work made of sound, words and space, dealing with the understanding of space and time in a very existential sense: it reflects upon perception and illumines the structures of individual memory.â : Isabell Hemmel, Walking in the limits, in: Tagesanzeiger Zurich, 17-8-2006 The stage space was based on a two year investigation into the supersymmetric string theory. In the case of string theory, consistency requires spacetime to have 10 (3+1+6) dimensions. The conflict between observation and theory is resolved by making the unobserved dimensions compactified. By simulating a biographical event staged over 24 hours in a hotel room in Berlin on the night that the wall fell on the 9 November 1989 and viewing these events in terms of the string theory we propose an 'observable' ten-dimensional simulation of the proposed reality offered by the string theory. Working closely with researchers at CERN in Geneva and the composer Heinz Reber the works seeks to make the invisible, visible and allow us to simulate the incomprehensible. The research goes further than illustrating a theory by proposing a new perspective on quantum physics through the disciplines of literature (Borges) Art (Wallen) and Music (Reber) by creating a fluid space in perpetual movement and ten differentiated space-time layers

Short-Term Synaptic Plasticity in the Dentate Gyrus of Monkeys

The hippocampus plays an important role in learning and memory. Synaptic plasticity in the hippocampus, short-term and long-term, is postulated to be a neural substrate of memory trace. Paired-pulse stimulation is a standard technique for evaluating a form of short-term synaptic plasticity in rodents. However, evidence is lacking for paired-pulse responses in the primate hippocampus. In the present study, we recorded paired-pulse responses in the dentate gyrus of monkeys while stimulating to the medial part of the perforant path at several inter-pulse intervals (IPIs) using low and high stimulus intensities. When the stimulus intensity was low, the first pulse produced early strong depression (at IPIs of 10–30 ms) and late slight depression (at IPIs of 100–1000 ms) of field excitatory postsynaptic potentials (fEPSPs) generated by the second pulse, interposing no depression IPIs (50–70 ms). When the stimulus intensity was high, fEPSPs generated by the second pulse were depressed by the first pulse at all IPIs except for the longest one (2000 ms). Population spikes (PSs) generated by the second pulse were completely blocked or strongly depressed at shorter IPIs (10–100 or 200 ms, respectively), while no depression or slight facilitation occurred at longer IPIs (500–2000 ms). Administration of diazepam slightly increased fEPSPs, while it decreased PSs produced by the first pulse. It also enhanced the facilitation of PSs produced by the second stimulation at longer IPIs. The present results, in comparison with previous studies using rodents, indicate that paired-pulse responses of fEPSPs in the monkey are basically similar to those of rodents, although paired-pulse responses of PSs in the monkey are more delayed than those in rodents and have a different sensitivity to diazepam

Does the Precision of a Biological Clock Depend upon Its Period? Effects of the Duper and tau Mutations in Syrian Hamsters

Mutations which alter the feedback loops that generate circadian rhythms may provide insight into their insensitivity to perturbation robustness) and their consistency of period (precision). I examined relationships between endogenous period, activity and rest (τDD, α and ρ) in Syrian hamsters using two different mutations, duper and tau, both of which speed up the circadian clock. I generated 8 strains of hamsters that are homozygous or heterozygous for the tau, duper, and wild type alleles in all combinations. The endogenous period of activity onsets among these strains ranged from 17.94+0.04 to 24.13±0.04 h. Contrary to predictions, the variability of period was unrelated to its absolute value: all strains showed similar variability of τDD when activity onsets and acrophase were used as phase markers. The τDD of activity offsets was more variable than onsets but also differed little between genotypes. Cycle variation and precision were not correlated with τDD within any strain, and only weakly correlated when all strains are considered together. Only in animals homozygous for both mutations (super duper hamsters) were cycle variation and precision reduced. Rhythm amplitude differed between strains and was positively correlated with τDD and precision. All genotypes showed negative correlations between α and ρ. This confirms the expectation that deviations in the duration of subjective day and night should offset one another in order to conserve circadian period, even though homeostatic maintenance of energy reserves predicts that longer intervals of activity or rest would be followed by longer durations of rest or activity. Females consistently showed greater variability of the period of activity onset and acrophase, and of α, but variability of the period of offset differed between sexes only in super duper hamsters. Despite the differences between genotypes in τDD, ρ was consistently more strongly correlated with the preceding than the succeeding α

Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells

Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells

Activated iNKT Cells Promote Memory CD8+ T Cell Differentiation during Viral Infection

α-galactosylceramide (α-GalCer) is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV). We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8+ T cells, as a consequence of reduced inflammation

NK Cell–Like Behavior of Vα14i NK T Cells during MCMV Infection

Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Vα14 invariant natural killer T cell response to MCMV has not been examined. We found that Vα14i NK T cells become activated and produce significant levels of IFN-γ, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Vα14i NK T cells into MCMV-infected CD1d−/− mice demonstrate that CD1d is dispensable for Vα14i NK T cell activation. In contrast, both IFN-α/β and IL-12 are required for optimal activation. Vα14i NK T cell–derived IFN-γ is partially dependent on IFN-α/β but highly dependent on IL-12. Vα14i NK T cells contribute to the immune response to MCMV and amplify NK cell–derived IFN-γ. Importantly, mortality is increased in CD1d−/− mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Vα14i NK T cells that act as effector T cells during bacterial infection, but have NK cell–like behavior during the innate immune response to MCMV infection