4,460 research outputs found
Sign reversal of the mixed-state Hall resistivity in type-II superconductors
Taking into account pinning, thermal fluctuations, and vortex-vortex interactions, we develop a unified theory to explain the sign reversal of the mixed-state Hall resistivity ρ xy in both high-T c and low-T c superconductors. Molecular dynamics simulations show that besides the pinning forces, either the thermal fluctuations in the high-T c superconductors or the vortex-vortex interactions in the low-T c ones play an important role in the sign reversal of ρ xy. From a calculated phase diagram for vortex motion, we find that the abnormal Hall effect always occurs in the plastic flow state of vortices. ©1999 The American Physical Society.published_or_final_versio
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The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.
Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology
Molecular basis for passive immunotherapy of Alzheimer's disease
Amyloid aggregates of the amyloid-{beta} (A{beta}) peptide are implicated in the pathology of Alzheimer's disease. Anti-A{beta} monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-A{beta} mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize A{beta} monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the A{beta}(1–8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to A{beta}(1–8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target A{beta} with improved specificity and higher affinity
Direct Heme Transfer Reactions in the Group A Streptococcus Heme Acquisition Pathway
The heme acquisition machinery in Group A Streptococcus (GAS) consists of the surface proteins Shr and Shp and ATP-binding cassette transporter HtsABC. Shp cannot directly acquire heme from methemoglobin (metHb) but directly transfers its heme to HtsA. It has not been previously determined whether Shr directly relays heme from metHb to Shp. Thus, the complete pathway for heme acquisition from metHb by the GAS heme acquisition machinery has remained unclear. In this study, the metHb-to-Shr and Shr-to-Shp heme transfer reactions were characterized by spectroscopy, kinetics and protein-protein interaction analyses. Heme is efficiently transferred from the β and α subunits of metHb to Shr with rates that are 7 and 60 times greater than those of the passive heme release from metHb, indicating that Shr directly acquires heme from metHb. The rapid heme transfer from Shr to Shp involves an initial heme donor/acceptor complex and a spectrally and kinetically detectable transfer intermediate, implying that heme is directly channeled from Shr to Shp. The present results show that Shr speeds up heme transfer from metHb to Shp, whereas Shp speeds up heme transfer from Shr to HtsA. Furthermore, the findings demonstrate that Shr can interact with metHb and Shp but not HtsA. Taken together with our published results on the Shp/HtsA reaction, these findings establish a model of the heme acquisition pathway in GAS in which Shr directly extracts heme from metHb and Shp relays it from Shr to HtsA
Back reaction, covariant anomaly and effective action
In the presence of back reaction, we first produce the one-loop corrections
for the event horizon and Hawking temperature of the Reissner-Nordstr\"om black
hole. Then, based on the covariant anomaly cancelation method and the effective
action technique, the modified expressions for the fluxes of gauge current and
energy momentum tensor, due to the effect of back reaction, are obtained. The
results are consistent with the Hawking fluxes of a (1+1)-dimensional blackbody
at the temperature with quantum corrections, thus confirming the robustness of
the covariant anomaly cancelation method and the effective action technique for
black holes with back reaction.Comment: 17 page
de Branges-Rovnyak spaces: basics and theory
For a contractive analytic operator-valued function on the unit disk
, de Branges and Rovnyak associate a Hilbert space of analytic
functions and related extension space
consisting of pairs of analytic functions on the unit disk . This
survey describes three equivalent formulations (the original geometric de
Branges-Rovnyak definition, the Toeplitz operator characterization, and the
characterization as a reproducing kernel Hilbert space) of the de
Branges-Rovnyak space , as well as its role as the underlying
Hilbert space for the modeling of completely non-isometric Hilbert-space
contraction operators. Also examined is the extension of these ideas to handle
the modeling of the more general class of completely nonunitary contraction
operators, where the more general two-component de Branges-Rovnyak model space
and associated overlapping spaces play key roles. Connections
with other function theory problems and applications are also discussed. More
recent applications to a variety of subsequent applications are given in a
companion survey article
CHY representations for gauge theory and gravity amplitudes with up to three massive particles
We show that a wide class of tree-level scattering amplitudes involving
scalars, gauge bosons, and gravitons, up to three of which may be massive, can
be expressed in terms of a Cachazo-He-Yuan representation as a sum over
solutions of the scattering equations. These amplitudes, when expressed in
terms of the appropriate kinematic invariants, are independent of the masses
and therefore identical to the corresponding massless amplitudes.Comment: 20 pages, 1 figure; v2: minor typos corrected, published versio
Back reaction, emission spectrum and entropy spectroscopy
Recently, an interesting work, which reformulates the tunneling framework to
directly produce the Hawking emission spectrum and entropy spectroscopy in the
tunneling picture, has been received a broad attention. However, during the
emission process, most related observations have not incorporated the effects
of back reaction on the background spacetime, whose derivations are therefore
not the desiring results for the real physical process. With this point as a
central motivation, in this paper we suitably adapt the \emph{reformulated}
tunneling framework so that it can well accommodate the effects of back
reaction to produce the Hawking emission spectrum and entropy spectroscopy.
Consequently, we interestingly find that, when back reaction is considered, the
Parikh-Wilczek's outstanding observations that, an isolated radiating black
hole has an unitary-evolving emission spectrum that is \emph{not} precisely
thermal, but is related to the change of the Bekenstein-Hawking entropy, can
also be reproduced in the reformulated tunneling framework, meanwhile the
entropy spectrum has the same form as that without inclusion of back reaction,
which demonstrates the entropy quantum is \emph{independent} of the effects of
back reaction. As our final analysis, we concentrate on the issues of the black
hole information, but \emph{unfortunately} find that, even including the
effects of back reaction and higher-order quantum corrections, such tunneling
formalism can still not provide a mechanism for preserving the black hole
information.Comment: 16 pages, no figure, use JHEP3.cls. to be published in JHE
Optogenetic Control of Subcellular Protein Location and Signaling in Vertebrate Embryos.
This chapter describes the use of optogenetic heterodimerization in single cells within whole-vertebrate embryos. This method allows the use of light to reversibly bind together an "anchor" protein and a "bait" protein. Proteins can therefore be directed to specific subcellular compartments, altering biological processes such as cell polarity and signaling. I detail methods for achieving transient expression of fusion proteins encoding the phytochrome heterodimerization system in early zebrafish embryos (Buckley et al., Dev Cell 36(1):117-126, 2016) and describe the imaging parameters used to achieve subcellular light patterning
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ADC Nonlinearity Correction for the Majorana Demonstrator
Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value
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