3,580 research outputs found
Remarks on the method of comparison equations (generalized WKB method) and the generalized Ermakov-Pinney equation
The connection between the method of comparison equations (generalized WKB
method) and the Ermakov-Pinney equation is established. A perturbative scheme
of solution of the generalized Ermakov-Pinney equation is developed and is
applied to the construction of perturbative series for second-order
differential equations with and without turning points.Comment: The collective of the authors is enlarged and the calculations in
Sec. 3 are correcte
Skeletal muscle cell protein dysregulation highlights the pathogenesis mechanism of myopathy-associated p97/VCP R155H mutations
p97/VCP, a hexametric member of the AAA-ATPase superfamily, has been associated with a wide range of cellular protein pathways, such as proteasomal degradation, the unfolding of polyubiquitinated proteins, and autophagosome maturation. Autosomal dominant p97/VCP mutations cause a rare hereditary multisystem disorder called IBMPFD/ALS (Inclusion Body Myopathy with Pagetâs Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis), characterized by progressive weakness and subsequent atrophy of skeletal muscles, and impacting bones and brains, such as Parkinsonâs disease, Lewy body disease, Huntingtonâs disease, and amyotrophic lateral ALS. Among all disease-causing mutations, Arginine 155 to Histidine (R155H/+) was reported to be the most common one, affecting over 50% of IBMPFD patients, resulting in disabling muscle weakness, which might eventually be life-threatening due to cardiac and respiratory muscle involvement. Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to study pathologyâs underlying molecular mechanism, perform drug screening, and investigate regeneration. Using R155H/+ patientsâ fibroblasts, we generated IPS cells and corrected the mutation (Histidine to Arginine, H155R) to generate isogenic control cells before differentiating them into myotubes. The further proteomic analysis allowed us to identify differentially expressed proteins associated with the R155H mutation. Our results showed that R155H/+ cells were associated with dysregulated expression of several proteins involved in skeletal muscle function, cytoskeleton organization, cell signaling, intracellular organelles organization and function, cell junction, and cell adhesion. Our findings provide molecular evidence of dysfunctional protein expression in R155H/+ myotubes and offer new therapeutic targets for treating IBMPFD/ALS
Progressive tauopathy in P301S tau transgenic mice is associated with a functional deficit of the olfactory system.
Multiple neurodegenerative disorders with tau pathology are characterised by the loss of memory and cognitive decline that can be associated with other symptoms including olfactory alterations that are often regarded as an early symptom of the diseases. Here, we have investigated whether olfactory dysfunction is present in the P301S human tau transgenic mice and if it is associated to tau pathology. Progressive tauopathy and neurodegeneration were noticeable in the olfactory bulb and piriform cortex at early age in the P301S human tau transgenic mice and olfactory sensitivity for social or non-social odours was significantly impaired at 3 months of age, when the piriform cortex-dependent odour-cross habituation was also disrupted. The olfactory alterations in the P301S tau transgenic mouse line provide an in vivo system where to test the mechanism-based therapies for the common and yet untreatable tauopathies.This work was supported by the European Union Framework 7 Project Plasticise (S.Y., M.G.S.) and the Alzheimerâs Research UK (M.G.S.).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/ejn.13333
Breakdown of the Endothelial Barrier Function in Tumor Cell Transmigration
The ability of tumor cells to metastasize is associated with a poor prognosis for cancer. During the process of metastasis, tumor cells circulating in the blood or lymph vessels can adhere to, and potentially transmigrate through, the endothelium and invade the connective tissue. We studied the effectiveness of the endothelium as a barrier against the invasion of 51 tumor cell lines into a three-dimensional collagen matrix. Only nine tumor cell lines showed attenuated invasion in the presence of an endothelial cell monolayer, whereas 17 cell lines became invasive or showed a significantly increased invasion. Endothelial cells cocultured with invasive tumor cells increased chemokine gene expression of IL-8 and Gro-ÎČ. Expression of the IL-8 and Gro-ÎČ receptor, CXCR2, was upregulated in invasive tumor cells. Addition of IL-8 or Gro-ÎČ increased tumor cell invasiveness by more than twofold. Tumor cell variants selected for high CXCR2 expression were fourfold more invasive in the presence of an endothelial cell layer, whereas CXCR2 siRNA knock-down cells were fivefold less invasive. We demonstrate that Gro-ÎČ and IL-8 secreted by endothelial cells, together with CXCR2 receptor expression on invasive tumor cells, contribute to the breakdown of the endothelial barrier by enhancing tumor cell force generation and cytoskeletal remodeling dynamics
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+Ï+Ï- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bcâ(2S31)+ state reconstructed without the low-energy photon from the Bcâ(1S31)+âBc+Îł decay following Bcâ(2S31)+âBcâ(1S31)+Ï+Ï-. A second state is seen with a global (local) statistical significance of 2.2Ï (3.2Ï) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) and the direct CP asymmetry in B0 -> K*0 gamma
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 phi gamma has been measured using an integrated luminosity of 1.0 fb-1
of pp collision data collected by the LHCb experiment at a centre-of-mass
energy of sqrt(s)=7 TeV. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 ->
phi gamma) = 1.23 +/- 0.06(stat.) +/- 0.04(syst.) +/- 0.10(fs/fd), where the
first uncertainty is statistical, the second is the experimental systematic
uncertainty and the third is associated with the ratio of fragmentation
fractions fs/fd. Using the world average value for BR(B0 -> K*0 gamma), the
branching fraction BR(Bs0 -> phi gamma) is measured to be (3.5 +/- 0.4) x
10^{-5}.
The direct CP asymmetry in B0 -> K*0 gamma decays has also been measured with
the same data and found to be A(CP)(B0 -> K*0 gamma) = (0.8 +/- 1.7(stat.) +/-
0.9(syst.))%.
Both measurements are the most precise to date and are in agreement with the
previous experimental results and theoretical expectations.Comment: 21 pages, 3 figues, 4 table
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
Opposite-side flavour tagging of B mesons at the LHCb experiment
The calibration and performance of the oppositeside
flavour tagging algorithms used for the measurements
of time-dependent asymmetries at the LHCb experiment
are described. The algorithms have been developed using
simulated events and optimized and calibrated with
B
+ âJ/ÏK
+, B0 âJ/ÏK
â0 and B0 âD
ââ
Ό
+
ΜΌ decay
modes with 0.37 fbâ1 of data collected in pp collisions
at
â
s = 7 TeV during the 2011 physics run. The oppositeside
tagging power is determined in the B
+ â J/ÏK
+
channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty
is statistical and the second is systematic
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