Noncommutative Instantons in 4k Dimensions

We consider Ward's generalized self-duality equations for U(2r) Yang-Mills theory on R^{4k} and their Moyal deformation under self-dual noncommutativity. Employing an extended ADHM construction we find two kinds of explicit solutions, which generalize the 't Hooft and BPST instantons from R^4 to noncommutative R^{4k}. The BPST-type configurations appear to be new even in the commutative case.Comment: 1+10 page

Double Field Theory Formulation of Heterotic Strings

We extend the recently constructed double field theory formulation of the low-energy theory of the closed bosonic string to the heterotic string. The action can be written in terms of a generalized metric that is a covariant tensor under O(D,D+n), where n denotes the number of gauge vectors, and n additional coordinates are introduced together with a covariant constraint that locally removes these new coordinates. For the abelian subsector, the action takes the same structural form as for the bosonic string, but based on the enlarged generalized metric, thereby featuring a global O(D,D+n) symmetry. After turning on non-abelian gauge couplings, this global symmetry is broken, but the action can still be written in a fully O(D,D+n) covariant fashion, in analogy to similar constructions in gauged supergravities.Comment: 28 pages, v2: minor changes, version published in JHE

Supertwistors and Cubic String Field Theory for Open N=2 Strings

The known Lorentz invariant string field theory for open N=2 strings is combined with a generalization of the twistor description of anti-self-dual (super) Yang-Mills theories. We introduce a Chern-Simons-type Lagrangian containing twistor variables and derive the Berkovits-Siegel covariant string field equations of motion via the twistor correspondence. Both the purely bosonic and the maximally space-time supersymmetric cases are considered.Comment: 1+9 pages; v2: minor clarification, 3 references added, published versio

The Ternary Rab27a–Myrip–Myosin VIIa Complex Regulates Melanosome Motility in the Retinal Pigment Epithelium

The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements in fish and amphibians. In mammals, those movements are more subtle and appear to be regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and MyoVIIa-interacting protein, Myrip, promotes the formation of a functional tripartite complex. In heterologous cultured cells, all three proteins co-immunoprecipitated following overexpression. Rab27a and Myrip localize to the peripheral membrane of RPE melanosomes as observed by immunofluorescence and immunoelectron microscopy. Melanosome dynamics were studied using live-cell imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either stationary or slow movement interrupted by bursts of fast movement, with a peripheral directionality trend. Nocodazole treatment led to melanosome paralysis, suggesting that movement requires microtubule motors. Significant and similar alterations in melanosome dynamics were observed when any one of the three components of the complex was missing, as studied in ashen- (Rab27a defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE cells transduced with adenovirus carrying specific sequences to knockdown Myrip expression. We observed a significant increase in the number of motile melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and inversion of directionality. Similar alterations were observed upon cytochalasin D treatment, suggesting that the Rab27a–Myrip–MyoVIIa complex regulates tethering of melanosomes onto actin filaments, a process that ensures melanosome movement towards the cell periphery

The adaptor molecule CARD9 is essential for tuberculosis control

The cross talk between host and pathogen starts with recognition of bacterial signatures through pattern recognition receptors (PRRs), which mobilize downstream signaling cascades. We investigated the role of the cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) in tuberculosis. This adaptor was critical for full activation of innate immunity by converging signals downstream of multiple PRRs. Card9−/− mice succumbed early after aerosol infection, with higher mycobacterial burden, pyogranulomatous pneumonia, accelerated granulocyte recruitment, and higher abundance of proinflammatory cytokines and granulocyte colony-stimulating factor (G-CSF) in serum and lung. Neutralization of G-CSF and neutrophil depletion significantly prolonged survival, indicating that an exacerbated systemic inflammatory disease triggered lethality of Card9−/− mice. CARD9 deficiency had no apparent effect on T cell responses, but a marked impact on the hematopoietic compartment. Card9−/− granulocytes failed to produce IL-10 after Mycobaterium tuberculosis infection, suggesting that an absent antiinflammatory feedback loop accounted for granulocyte-dominated pathology, uncontrolled bacterial replication, and, ultimately, death of infected Card9−/− mice. Our data provide evidence that deregulated innate responses trigger excessive lung inflammation and demonstrate a pivotal role of CARD9 signaling in autonomous innate host defense against tuberculosis

Development of Micro-Electrode Array Based Tests for Neurotoxicity: Assessment of Interlaboratory Reproducibility with Neuroactive Chemicals

Neuronal assemblies within the nervous system produce electrical activity that can be recorded in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of a variety of chemical and physical perturbations. They are a function of synaptic changes and do not necessarily involve structural alterations. In vitro neuronal networks (NNs) grown on micro-electrode arrays (MEAs) respond to neuroactive substances as well as the in vivo brain. As such, they constitute a valuable tool for investigating changes in the electrophysiological activity of the neurons in response to chemical exposures. However, the reproducibility of NN responses to chemical exposure has not been systematically documented. To this purpose six independent laboratories (in Europe and in USA) evaluated the response to the same pharmacological compounds (Fluoxetine, Muscimol, and Verapamil) in primary neuronal cultures. Common standardization principles and acceptance criteria for the quality of the cultures have been established to compare the obtained results. These studies involved more than 100 experiments before the final conclusions have been drawn that MEA technology has a potential for standard in vitro neurotoxicity/neuropharmacology evaluation. The obtained results show good intra- and inter-laboratory reproducibility of the responses. The consistent inhibitory effects of the compounds were observed in all the laboratories with the 50% Inhibiting Concentrations (IC50s) ranging from: (mean ± SEM, in μM) 1.53 ± 0.17 to 5.4 ± 0.7 (n = 35) for Fluoxetine, 0.16 ± 0.03 to 0.38 ± 0.16 μM (n = 35) for Muscimol, and 2.68 ± 0.32 to 5.23 ± 1.7 (n = 32) for Verapamil. The outcome of this study indicates that the MEA approach is a robust tool leading to reproducible results. The future direction will be to extend the set of testing compounds and to propose the MEA approach as a standard screen for identification and prioritization of chemicals with neurotoxicity potential

Social acceptance of renewable energy: Some examples from Europe and Developing Africa

Current energy systems are in most instances not fully working sustainably. The provision and use of energy only consider limited resources, risk potential or financial constraints on a limited scale. Furthermore, the knowledge and benefits are only available for a minor group of the population or are outright neglected. The availability of different resources for energy purposes determines economic development, as well as the status of the society and the environment. The access to energy grids has an impact on socio-economic living standards of communities. This not fully developed system is causing climate change with all its related outcomes. This investigation takes into consideration different views on renewable energy systems — such as international discussions about biomass use for energy production, “fuel versus food”, biogas use — and attempts to compare major prospects of social acceptance of renewable energy in Europe and Africa. Can all obstacles to the use of renewable energy be so profound that the overall strategy of reducing anthropogenic causes of climate change be seriously affected

Subspace Projection Approaches to Classification and Visualization of Neural Network-Level Encoding Patterns

Recent advances in large-scale ensemble recordings allow monitoring of activity patterns of several hundreds of neurons in freely behaving animals. The emergence of such high-dimensional datasets poses challenges for the identification and analysis of dynamical network patterns. While several types of multivariate statistical methods have been used for integrating responses from multiple neurons, their effectiveness in pattern classification and predictive power has not been compared in a direct and systematic manner. Here we systematically employed a series of projection methods, such as Multiple Discriminant Analysis (MDA), Principal Components Analysis (PCA) and Artificial Neural Networks (ANN), and compared them with non-projection multivariate statistical methods such as Multivariate Gaussian Distributions (MGD). Our analyses of hippocampal data recorded during episodic memory events and cortical data simulated during face perception or arm movements illustrate how low-dimensional encoding subspaces can reveal the existence of network-level ensemble representations. We show how the use of regularization methods can prevent these statistical methods from over-fitting of training data sets when the trial numbers are much smaller than the number of recorded units. Moreover, we investigated the extent to which the computations implemented by the projection methods reflect the underlying hierarchical properties of the neural populations. Based on their ability to extract the essential features for pattern classification, we conclude that the typical performance ranking of these methods on under-sampled neural data of large dimension is MDA>PCA>ANN>MGD