1,935 research outputs found
Effects of ferumoxytol on quantitative PET measurements in simultaneous PET/MR whole-body imaging: a pilot study in a baboon model.
BACKGROUND
Simultaneous PET/MR imaging depends on MR-derived attenuation maps (mu-maps) for accurate attenuation correction of PET data. Currently, these maps are derived from gradient-echo-based MR sequences, which are sensitive to susceptibility changes. Iron oxide magnetic nanoparticles have been used in the measurement of blood volume, tumor microvasculature, tumor-associated macrophages, and characterizing lymph nodes. Our aim in this study was to assess whether the susceptibility effects associated with iron oxide nanoparticles can potentially affect measured (18)F-FDG PET standardized uptake values (SUV) through effects on MR-derived attenuation maps.
METHODS
The study protocol was approved by the Institutional Animal Care and Use Committee. Using a Siemens Biograph mMR PET/MR scanner, we evaluated the effects of increasing concentrations of ferumoxytol and ferumoxytol aggregates on MR-derived mu-maps using an agarose phantom. In addition, we performed a baboon experiment evaluating the effects of a single i.v. ferumoxytol dose (10Â mg/kg) on the liver, spleen, and pancreas (18)F-FDG SUV at baseline (ferumoxytol-naĂŻve), within the first hour and at 1, 3, 5, and 11Â weeks.
RESULTS
Phantom experiments showed mu-map artifacts starting at ferumoxytol aggregate concentrations of 10 to 20Â mg/kg. The in vivo baboon data demonstrated a 53% decrease of observed (18)F-FDG SUV compared to baseline within the first hour in the liver, persisting at least 11Â weeks.
CONCLUSIONS
A single ferumoxytol dose can affect measured SUV for at least 3Â months, which should be taken into account when administrating ferumoxytol in patients needing sequential PET/MR scans. Advances in knowledge 1. Ferumoxytol aggregates, but not ferumoxytol alone, produce significant artifacts in MR-derived attenuation correction maps at approximate clinical dose levels of 10Â mg/kg. 2. When performing simultaneous whole-body (18)F-FDG PET/MR, a single dose of ferumoxytol can result in observed SUV decreases up to 53%, depending on the amount of ferumoxytol aggregates in the studied tissue. Implications for patient care Administration of a single, clinically relevant, dose of ferumoxytol can potentially result in changes in observed SUV for a prolonged period of time in the setting of simultaneous PET/MR. These potential changes should be considered in particular when administering ferumoxytol to patients with expected future PET/MR studies, as ferumoxytol-induced SUV changes might interfere with therapy assessment
Deletion of the mRNA Stability Factor ELAVL1 (HuR) In Pancreatic Cancer Cells Disrupts the Tumor Microenvironment Integrity
Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, αsmooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cellâcell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of signaling molecules involved in stromal activation and extracellular matrix organization [i.e. platelet-derived growth factor AA (PDGFAA) and pentraxin 3]. Ribonucleoprotein immunoprecipitation analysis and transcription inhibition studies validated PDGFA mRNA as a novel HuR target. These data suggest that tumor-intrinsic HuR supports extrinsic activation of the stroma to produce collagen and desmoplasia through regulating signaling molecules (e.g. PDGFAA). HuR-deficient PDAC in vivo tumors with an altered tumor microenvironment are more sensitive to the standard of care gemcitabine, as compared to HuR-proficient tumors. Taken together, we identified a novel role of tumor-intrinsic HuR in its ability to modify the surrounding tumor microenvironment and regulate PDGFAA
A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-ÎșB
The development of forward genetic screens in human haploid cells has the potential to transform our understanding of the genetic basis of cellular processes unique to man. So far, this approach has been limited mostly to the identification of genes that mediate cell death in response to a lethal agent, likely due to the ease with which this phenotype can be observed. Here, we perform the first reporter screen in the near-haploid KBM7 cell line to identify constitutive inhibitors of NF-ÎșB. CYLD was the only currently known negative regulator of NF-ÎșB to be identified, thus uniquely distinguishing this gene. Also identified were three genes with no previous known connection to NF-ÎșB. Our results demonstrate that reporter screens in haploid human cells can be applied to investigate the many complex signaling pathways that converge upon transcription factors
Differential branching fraction and angular analysis of the decay B0âKâ0ÎŒ+ÎŒâ
The angular distribution and differential branching fraction of the decay B 0â K â0 ÎŒ + ÎŒ â are studied using a data sample, collected by the LHCb experiment in pp collisions at sâ=7 TeV, corresponding to an integrated luminosity of 1.0 fbâ1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
Measurement of the CKM angle Îł from a combination of B±âDh± analyses
A combination of three LHCb measurements of the CKM angle Îł is presented. The decays B±âD K± and
B±âDϱ are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+Kâ, Ï+Ïâ, K±Ïâ, K±ÏâϱÏâ, K0SÏ+Ïâ, or K0S K+Kâ ïŹnal states. All measurements use a dataset corresponding to 1.0 fbâ1 of integrated luminosity. Combining results from B±âD K± decays alone a best-ïŹt value of
Îł =72.0⊠is found, and conïŹdence intervals are set
Îł â [56.4,86.7]⊠at 68% CL,
Îł â [42.6,99.6]⊠at 95% CL.
The best-ïŹt value of Îł found from a combination of results from B±âDϱ decays alone, is Îł =18.9âŠ,
and the conïŹdence intervals
Îł â [7.4,99.2]⊠âȘ [167.9,176.4]⊠at 68% CL
are set, without constraint at 95% CL. The combination of results from B± â D K± and B± â Dϱ
decays gives a best-ïŹt value of Îł =72.6⊠and the conïŹdence intervals
Îł â [55.4,82.3]⊠at 68% CL,
Îł â [40.2,92.7]⊠at 95% CL
are set. All values are expressed modulo 180âŠ, and are obtained taking into account the effect of D0âD0
mixing
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
Measurements of the , , meson and baryon lifetimes
Measurements of -hadron lifetimes are reported using collision data,
corresponding to an integrated luminosity of 1.0fb, collected by the
LHCb detector at a centre-of-mass energy of Tev. Using the exclusive decays
, , ,
and the average decay
times in these modes are measured to be = 0.004 0.003 ps, =
0.006 0.004 ps, = 0.013
0.005 ps, = 0.027
0.006 ps and = 0.011
0.005 ps, where the first uncertainty is statistical and the second is
systematic. These represent the most precise lifetime measurements in these
decay modes. In addition, ratios of these lifetimes, and the ratio of the
decay-width difference, , to the average width, , in
the system, , are
reported. All quantities are found to be consistent with Standard Model
expectations.Comment: 28 pages, 4 figures. Updated reference
Measurement of the relative rate of prompt Ïc0, Ïc1 and Ïc2 production at âs=7TeV
Prompt production of charmonium Ïc0, Ïc1 and Ïc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of âs=7TeV. The Ïc mesons are identified through their decay to J/ÏÎł, with J/ÏâÎŒ+muâ using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fbâ1 collected by the LHCb detector, is used to measure the relative prompt production rate of Ïc1 and Ïc2 in the rapidity range 2.0<y<4.5 as a function of the J/Ï transverse momentum from 3 to 20 GeV/c. First evidence for Ïc0 meson production at a hadron collider is also presented
Study of DJ meson decays to D+Ïâ, D0Ï+ and Dâ+Ïâ final states in pp collisions
A study of D+Ïâ, D0Ï+ and Dâ+Ïâ final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fbâ1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D1(2420)0 resonance is observed in the Dâ+Ïâ final state and the Dâ2(2460) resonance is observed in the D+Ïâ, D0Ï+ and Dâ+Ïâ final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the Dâ+Ïâ, D+Ïâ and D0Ï+ final states
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