567 research outputs found
SNX27 and SORLA interact to reduce amyloidogenic subcellular distribution and processing of amyloid precursor protein
Proteolytic generation of amyloidogenic amyloid {beta} (A{beta}) fragments from the amyloid precursor protein (APP) significantly contributes to Alzheimer's disease (AD). Although amyloidogenic APP proteolysis can be affected by trafficking through genetically associated AD components such as SORLA, how SORLA functionally interacts with other trafficking components is yet unclear. Here, we report that SNX27, an endosomal trafficking/recycling factor and a negative regulator of the {gamma}-secretase complex, binds to the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell surface SORLA and APP levels in human cell lines and mouse primary neurons, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances the generation of cell surface APP cleavage products such as soluble alpha-APP C-terminal fragment (CTF{alpha}) in a SORLA-dependent manner. SORLA-mediated A{beta} reduction is attenuated by downregulation of SNX27. This indicates that an SNX27/SORLA complex functionally interacts to limit APP distribution to amyloidogenic compartments, forming a non-amyloidogenic shunt to promote APP recycling to the cell surface
Liver resection rate following downsizing chemotherapy with cetuximab in metastatic colorectal cancer: UK retrospective observational study
Aims The high objective response rate to cetuximab along with chemotherapy in patients with colorectal liver metastases makes it an effective downsizing protocol to facilitate surgery in those with initially unresectable disease. Adoption of this strategy has been variable in the UK. A retrospective observational study was conducted in 7 UK specialist liver surgical centres to describe the liver resection rate following a downsizing protocol of cetuximab and chemotherapy and to evaluate the quality and efficiency of processes by which the treatment was provided. Methods Data were collected in 2012 by reviewing medical records of patients with colorectal metastases confined to the liver, defined as unresectable without downsizing therapy at first review by a specialist Multi Disciplinary Team (MDT). Results Sixty patients were included; 29 (48%) underwent liver resection following cetuximab and chemotherapy. Of the 29, 17 (59% or 28% of all patients) achieved R0 resection and 7 (24% or 12% of all patients) R1 resection. All treated patients were KRAS wild-type. Conclusion In specialist liver surgical centres, where patients are evaluated for liver resection, optimal management by MDT using KRAS testing, cetuximab and chemotherapy results in a 28% R0 resection rate in patients with initially unresectable colorectal cancer liver metastases
Asymptotic Giant Branch Variables in the Galaxy and the Local Group
AGB variables, particularly the large amplitude Mira type, are a vital step
on the distance scale ladder. They will prove particularly important in the era
of space telescopes and extremely large ground-based telescopes with adaptive
optics, which will be optimized for infrared observing. Our current
understanding of the distances to these stars is reviewed with particular
emphasis on improvements that came from Hipparcos as well as on recent work on
Local Group galaxies. In addition to providing the essential calibration for
extragalactic distances Gaia may also provide unprecedented insight into the
poorly understood mass-loss process itself.Comment: Accepted for publication in Astrophysics and Space Science. From a
presentation at the conference "The Fundamental Cosmic Distance Scale: State
of the Art and Gaia Perspective, Naples May 2011. 8 Pages, 9 Figure
Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV
A search for pair-production of supersymmetric particles under the assumption
that R-parity is violated via a dominant LQDbar coupling has been performed
using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV.
The observed candidate events in the data are in agreement with the Standard
Model expectation. This result is translated into lower limits on the masses of
charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for
m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81
GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the
95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure
Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV
Results are presented from a search for a W' boson using a dataset
corresponding to 5.0 inverse femtobarns of integrated luminosity collected
during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV.
The W' boson is modeled as a heavy W boson, but different scenarios for the
couplings to fermions are considered, involving both left-handed and
right-handed chiral projections of the fermions, as well as an arbitrary
mixture of the two. The search is performed in the decay channel W' to t b,
leading to a final state signature with a single lepton (e, mu), missing
transverse energy, and jets, at least one of which is tagged as a b-jet. A W'
boson that couples to fermions with the same coupling constant as the W, but to
the right-handed rather than left-handed chiral projections, is excluded for
masses below 1.85 TeV at the 95% confidence level. For the first time using LHC
data, constraints on the W' gauge coupling for a set of left- and right-handed
coupling combinations have been placed. These results represent a significant
improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe
Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV
A search for a Higgs boson decaying into two photons is described. The
analysis is performed using a dataset recorded by the CMS experiment at the LHC
from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an
integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross
section of the standard model Higgs boson decaying to two photons. The expected
exclusion limit at 95% confidence level is between 1.4 and 2.4 times the
standard model cross section in the mass range between 110 and 150 GeV. The
analysis of the data excludes, at 95% confidence level, the standard model
Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The
largest excess of events above the expected standard model background is
observed for a Higgs boson mass hypothesis of 124 GeV with a local significance
of 3.1 sigma. The global significance of observing an excess with a local
significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is
estimated to be 1.8 sigma. More data are required to ascertain the origin of
this excess.Comment: Submitted to Physics Letters
Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV
The Lambda(b) differential production cross section and the cross section
ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum
pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7
TeV using data collected by the CMS experiment at the LHC. The measurements are
based on Lambda(b) decays reconstructed in the exclusive final state J/Psi
Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and
Lambda to proton pion, using a data sample corresponding to an integrated
luminosity of 1.9 inverse femtobarns. The product of the cross section times
the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls
faster than that of b mesons. The measured value of the cross section times the
branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06
+/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for
anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are
statistical and systematic, respectively.Comment: Submitted to Physics Letters
Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV
A search is presented for physics beyond the standard model (BSM) in final
states with a pair of opposite-sign isolated leptons accompanied by jets and
missing transverse energy. The search uses LHC data recorded at a
center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to
an integrated luminosity of approximately 5 inverse femtobarns. Two
complementary search strategies are employed. The first probes models with a
specific dilepton production mechanism that leads to a characteristic kinematic
edge in the dilepton mass distribution. The second strategy probes models of
dilepton production with heavy, colored objects that decay to final states
including invisible particles, leading to very large hadronic activity and
missing transverse energy. No evidence for an event yield in excess of the
standard model expectations is found. Upper limits on the BSM contributions to
the signal regions are deduced from the results, which are used to exclude a
region of the parameter space of the constrained minimal supersymmetric
extension of the standard model. Additional information related to detector
efficiencies and response is provided to allow testing specific models of BSM
physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO
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