697 research outputs found
The Chern character of {\theta}-summable Fredholm modules over dg algebras and localization on loop space
We introduce the notion of a {\vartheta}-summable Fredholm module over a locally convex dg algebra {\Omega} and construct its Chern character as a cocycle on the entire cyclic complex of {\Omega}, extending the construction of Jaffe, Lesniewski and Osterwalder to a differential graded setting. Using this Chern character, we prove an index theorem involving an abstract version of a Bismut-Chern character constructed by Getzler, Jones and Petrack in the context of loop spaces. Our theory leads to a rigorous construction of the path integral for N=1/2 supersymmetry which satisfies a Duistermaat-Heckman type localization formula on loop space
An evaluation of the ATM man/machine interface. Phase 3: Analysis of SL-3 and SL-4 data
The functional adequacy of human factored crew operated systems under operational zero-gravity conditions is considered. Skylab ATM experiment operations generated sufficient telemetry and voice transcript data to support such an assessment effort. Discussions are presented pertaining to the methodology and procedures used to evaluate the hardware, training and directive aspects of Skylab 3 and Skylab 4 manned ATM experiment operations
Phase-sensitive detection of Bragg scattering at 1D optical lattices
We report on the observation of Bragg scattering at 1D atomic lattices. Cold
atoms are confined by optical dipole forces at the antinodes of a standing wave
generated by the two counter-propagating modes of a laser-driven high-finesse
ring cavity. By heterodyning the Bragg-scattered light with a reference beam,
we obtain detailed information on phase shifts imparted by the Bragg scattering
process. Being deep in the Lamb-Dicke regime, the scattered light is not
broadened by the motion of individual atoms. In contrast, we have detected
signatures of global translatory motion of the atomic grating.Comment: 4 pages, 4 figure
Bouncing trimer: a random self-propelled particle, chaos and periodical motions
A trimer is an object composed of three centimetrical stainless steel beads
equally distant and is predestined to show richer behaviours than the bouncing
ball or the bouncing dimer. The rigid trimer has been placed on a plate of a
electromagnetic shaker and has been vertically vibrated according to a
sinusoidal signal. The horizontal translational and rotational motions of the
trimer have been recorded for a range of frequencies between 25 and 100 Hz
while the amplitude of the forcing vibration was tuned for obtaining maximal
acceleration of the plate up to 10 times the gravity. Several modes have been
detected like e.g. rotational and pure translational motions. These modes are
found at determined accelerations of the plate and do not depend on the
frequency. By recording the time delays between two successive contacts when
the frequency and the amplitude are fixed, a mapping of the bouncing regime has
been constructed and compared to that of the dimer and the bouncing ball.
Period-2 and period-3 orbits have been experimentally observed. In these modes,
according to observations, the contact between the trimer and the plate is
persistent between two successive jumps. This persistence erases the memory of
the jump preceding the contact. A model is proposed and allows to explain the
values of the particular accelerations for which period-2 and period-3 modes
are observed. Finally, numerical simulations allow to reproduce the
experimental results. That allows to conclude that the friction between the
beads and the plate is the major dissipative process.Comment: 22 pages, 10 figure
Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis.
Lymphatic growth (lymphangiogenesis) within lymph nodes functions to promote dendritic cell entry and effector lymphocyte egress in response to infection or inflammation. Here we demonstrate a crucial role for lymphotoxin-beta receptor (LTβR) signaling to fibroblastic reticular cells (FRCs) by lymphotoxin-expressing B cells in driving mesenteric lymph node lymphangiogenesis following helminth infection. LTβR ligation on fibroblastic reticular cells leads to the production of B-cell-activating factor (BAFF), which synergized with interleukin-4 (IL-4) to promote the production of the lymphangiogenic factors, vascular endothelial growth factors (VEGF)-A and VEGF-C, by B cells. In addition, the BAFF-IL-4 synergy augments expression of lymphotoxin by antigen-activated B cells, promoting further B cell-fibroblastic reticular cell interactions. These results underlie the importance of lymphotoxin-dependent B cell-FRC cross talk in driving the expansion of lymphatic networks that function to promote and maintain immune responsiveness.The growth of lymph nodes in response to infection requires lymphangiogenesis. Dubey et al. show that the mesenteric lymph node lymphangiogenesis upon helminth infection depends on the signaling loop between the B and fibroblastic reticular cells (FRCs), whereby the FRCs respond to lymphotoxin secreted by B cells by releasing B cell activating factor
IL-4Rα-Expressing B Cells Are Required for CXCL13 Production by Fibroblastic Reticular Cells.
Adaptive type 2 immune responses against the intestinal helminth Heligmosomoides polygyrus (Hp) require the interaction of follicle-associated CXCR5 <sup>+</sup> dendritic cells with naive T cells in the draining mesenteric lymph nodes (mLNs). However, the source of CXCL13 responsible for attracting CXCR5 <sup>+</sup> dendritic cells has remained unclear. Using multiplex imaging combined with deep tissue analysis, we observed new CXCL13 <sup>+</sup> fibroblastic reticular cells surrounding paracortical and cortical B cell follicles in the mLNs of infected mice. CXCL13 <sup>+</sup> fibroblasts expressed markers of marginal reticular cells (MRCs), and their expansion required lymphotoxin (LT)-dependent interactions between IL-4Rα-expressing B cells and CCL19 <sup>+</sup> fibroblasts. Infection-induced follicles did not necessarily contain follicular dendritic cells (FDCs), indicating that CXCL13 <sup>+</sup> fibroblasts may instead drive their formation. These data reveal a role for lymphotoxin signaling to CCL19 <sup>+</sup> fibroblasts in the development of CXCL13 <sup>+</sup> MRC-like cells and adaptive type 2 immunity in response to helminth infection
A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans
Small molecule metabolites play important roles in Caenorhabditis elegans biology, but effective approaches for identifying their chemical structures are lacking. Recent studies revealed that a family of glycosides, the ascarosides, differentially regulate C. elegans development and behavior. Low concentrations of ascarosides attract males and thus appear to be part of the C. elegans sex pheromone, whereas higher concentrations induce developmental arrest at the dauer stage, an alternative, nonaging larval stage. The ascarosides act synergistically, which presented challenges for their identification via traditional activity-guided fractionation. As a result the chemical characterization of the dauer and male attracting pheromones remained incomplete. Here, we describe the identification of several additional pheromone components by using a recently developed NMR-spectroscopic approach, differential analysis by 2D NMR spectroscopy (DANS), which simplifies linking small molecule metabolites with their biological function. DANS-based comparison of wild-type C. elegans and a signaling-deficient mutant, daf-22, enabled identification of 3 known and 4 previously undescribed ascarosides, including a compound that features a p-aminobenzoic acid subunit. Biological testing of synthetic samples of these compounds revealed additional evidence for synergy and provided insights into structure–activity relationships. Using a combination of the three most active ascarosides allowed full reconstitution of the male-attracting activity of wild-type pheromone extract. Our results highlight the efficacy of DANS as a method for identifying small-molecule metabolites and placing them within a specific genetic context. This study further supports the hypothesis that ascarosides represent a structurally diverse set of nematode signaling molecules regulating major life history traits
Immunomodulation of Myocardial Fibrosis
Immunotherapy is a potential cornerstone in the treatment of myocardial fibrosis. During a myocardial insult or heart failure, danger signals stimulate innate immune cells to produce chemokines and profibrotic cytokines, which initiate self-escalating inflammatory processes by attracting and stimulating adaptive immune cells. Stimulation of fibroblasts by inflammatory processes and the need to replace damaged cardiomyocytes fosters reshaping of the cardiac fibroblast landscape. In this review, we discuss new immunomodulatory strategies that manipulate and direct cardiac fibroblast activation and differentiation. In particular, we highlight immunomodulatory strategies that target fibroblasts such as chimeric antigen receptor T cells, interleukin-11, and invariant natural killer T-cells. Moreover, we discuss the potential of manipulating both innate and adaptive immune system components for the translation into clinical validation. Clearly, multiple pathways should be considered to develop innovative approaches to ameliorate myocardial fibrosis and hence to reduce the risk of heart failure
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