High Resolution Polar Kerr Effect Measurements of Sr2RuO4: Evidence for Broken Time Reversal Symmetry in the Superconducting State

Polar Kerr effect in the spin-triplet superconductor Sr2RuO4 was measured with high precision using a Sagnac interferometer with a zero-area Sagnac loop. We observed non-zero Kerr rotations as big as 65 nanorad appearing below Tc in large domains. Our results imply a broken time reversal symmetry state in the superconducting state of Sr2RuO4, similar to He3-A

Development of a frequency-detuned interferometer as a prototype experiment for next-generation gravitational-wave detectors

We report on our prototype experiment that uses a 4-m detuned resonant sideband extraction interferometer with suspended mirrors, which has almost the same configuration as the next-generation, gravitational-wave detectors. We have developed a new control scheme and have succeeded in the operation of such an interferometer with suspended mirrors for the first time ever as far as we know. We believe that this is the first such instrument that can see the radiation pressure signal enhancement, which can improve the sensitivity of next-generation gravitational-wave detectors

Adaptive thermal compensation of test masses in advanced LIGO

As the first generation of laser interferometric gravitational wave detectors near operation, research and development has begun on increasing the instrument's sensitivity while utilizing the existing infrastructure. In the Laser Interferometer Gravitational Wave Observatory (LIGO), significant improvements are being planned for installation in ~2007, increasing strain sensitivity through improved suspensions and test mass substrates, active seismic isolation, and higher input laser power. Even with the highest quality optics available today, however, finite absorption of laser power within transmissive optics, coupled with the tremendous amount of optical power circulating in various parts of the interferometer, result in critical wavefront deformations which would cripple the performance of the instrument. Discussed is a method of active wavefront correction via direct thermal actuation on optical elements of the interferometer. A simple nichrome heating element suspended off the face of an affected optic will, through radiative heating, remove the gross axisymmetric part of the original thermal distortion. A scanning heating laser will then be used to remove any remaining non-axisymmetric wavefront distortion, generated by inhomogeneities in the substrate's absorption, thermal conductivity, etc. A proof-of-principle experiment has been constructed at MIT, selected data of which are presented.Comment: 11 pages, 7 figures, submitted to Classical and Quantum Gravit

Direct binding of the pH-regulated protein 1 (Pra1) from Candida albicans inhibits cytokine secretion by mouse CD4+ T cells

Opportunistic infections with the saprophytic yeast Candida albicans are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. In particular, direct interaction of proteins secreted by C. albicans with CD4+ T cells has not been studied in detail. In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4+ T cells in vitro. Binding of Pra1 to the T cell surface was enhanced by extracellular Zn2+ ions which Pra1 is known to scavenge from the host in order to supply the fungus with Zn2+. In vitro stimulation assays using highly purified mouse CD4+ T cells showed that Pra1 increased proliferation of CD4+ T cells in the presence of plate-bound anti-CD3 monoclonal antibody. In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4+ T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4+ T cell responses as shown in our in vitro assays

The Cape Town Declaration on access to cardiac surgery in the developing world

The mission of this declaration is to urge all relevant entities within the international cardiac surgery, industry, and government sectors to commit to develop and implement an effective strategy to address the scourge of rheumatic heart disease in the developing world through increased access to lifesaving cardiac surgery

Garcinolic Acid Distinguishes Between GACKIX Domains and Modulates Interaction Networks

Natural products are often uniquely suited to modulate protein-protein interactions (PPIs) due to their architectural and functional group complexity relative to synthetic molecules. Here we demonstrate that the natural product garcinolic acid allosterically blocks the CBP/p300 KIX PPI network and displays excellent selectivity over related GACKIX motifs. It does so via a strong interaction (KD 1 μM) with a non-canonical binding site containing a structurally dynamic loop in CBP/p300 KIX. Garcinolic acid engages full-length CBP in the context of the proteome and in doing so effectively inhibits KIX-dependent transcription in a leukemia model. As the most potent small-molecule KIX inhibitor yet reported, garcinolic acid represents an important step forward in the therapeutic targeting of CBP/p300

Signaling Signatures and Functional Properties of Anti-Human CD28 Superagonistic Antibodies

Superagonistic CD28 antibodies (CD28SAs) activate T lymphocytes without concomitant perturbation of the TCR/CD3-complex. In rodents these reagents induce the preferential expansion of regulatory T cells and can be used for the treatment of autoimmune diseases. Unexpectedly, the humanized CD28 superagonist TGN1412 caused severe and life threatening adverse effects during a recently conducted phase I clinical trail. The underlying molecular mechanisms are as yet unclear. We show that TGN1412 as well as the commercially available CD28 superagonist ANC28.1 induce a delayed but extremely sustained calcium response in human naïve and memory CD4+ T cells but not in cynomolgus T lymphocytes. The sustained Ca++-signal was associated with the activation of multiple intracellular signaling pathways and together these events culminated in the rapid de novo synthesis of high amounts of pro-inflammatory cytokines, most notably IFN-γ and TNF-α. Importantly, sustained transmembranous calcium flux, activation of Src-kinases as well as activation of PI3K were found to be absolutely required for CD28SA-mediated production of IFN-γ and IL-2. Collectively, our data suggest a molecular basis for the severe side effects caused by TGN1412 and impinge upon the relevance of non-human primates as preclinical models for reagents that are supposed to modify the function of human T cells