33 research outputs found
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
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
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
Coincidence analysis to search for inspiraling compact binaries using TAMA300 and LISM data
Japanese laser interferometric gravitational wave detectors, TAMA300 and
LISM, performed a coincident observation during 2001. We perform a coincidence
analysis to search for inspiraling compact binaries. The length of data used
for the coincidence analysis is 275 hours when both TAMA300 and LISM detectors
are operated simultaneously. TAMA300 and LISM data are analyzed by matched
filtering, and candidates for gravitational wave events are obtained. If there
is a true gravitational wave signal, it should appear in both data of detectors
with consistent waveforms characterized by masses of stars, amplitude of the
signal, the coalescence time and so on. We introduce a set of coincidence
conditions of the parameters, and search for coincident events. This procedure
reduces the number of fake events considerably, by a factor
compared with the number of fake events in single detector analysis. We find
that the number of events after imposing the coincidence conditions is
consistent with the number of accidental coincidences produced purely by noise.
We thus find no evidence of gravitational wave signals. We obtain an upper
limit of 0.046 /hours (CL ) to the Galactic event rate within 1kpc from
the Earth. The method used in this paper can be applied straightforwardly to
the case of coincidence observations with more than two detectors with
arbitrary arm directions.Comment: 28 pages, 17 figures, Replaced with the version to be published in
Physical Review
Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004
We analyze the data of TAMA300 detector to search for gravitational waves
from inspiraling compact star binaries with masses of the component stars in
the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the
years 2000-2004, are used for the event search. We combine the results of
different observation runs, and obtained a single upper limit on the rate of
the coalescence of compact binaries in our Galaxy of 20 per year at a 90%
confidence level. In this upper limit, the effect of various systematic errors
such like the uncertainty of the background estimation and the calibration of
the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was
correcte
Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis
Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development