LES of non-Newtonian physiological blood flow in a model of arterial stenosis

Large Eddy Simulation (LES) is performed to study the physiological pulsatile transition-to-turbulent non-Newtonian blood flow through a 3D model of arterial stenosis by using five different blood viscosity models: (i) Power-law, (ii) Carreau, (iii) Quemada, (iv) Cross and (v) modified-Casson. The computational domain has been chosen is a simple channel with a biological type stenosis formed eccentrically on the top wall. The physiological pulsation is generated at the inlet of the model using the first four harmonic series of the physiological pressure pulse (Loudon and Tordesillas [1]). The effects of the various viscosity models are investigated in terms of the global maximum shear rate, post-stenotic re-circulation zone, mean shear stress, mean pressure, and turbulent kinetic energy. We find that the non-Newtonian viscosity models enlarge the length of the post-stenotic re-circulation region by moving the reattachment point of the shear layer separating from the upper wall further downstream. But the turbulent kinetic energy at the immediate post-lip of the stenosis drops due to the effects of the non-Newtonian viscosity. The importance of using LES in modelling the non-Newtonian physiological pulsatile blood flow is also assessed for the different viscosity models in terms of the results of the dynamic subgrid-scale (SGS) stress Smagorinsky model constant, C<sub>s</sub>, and the corresponding SGS normalised viscosity

Investigation of physiological pulsatile flow in a model arterial stenosis using large-eddy and direct numerical simulations

Physiologicalpulsatileflow in a 3D model of arterialstenosis is investigated by using largeeddysimulation (LES) technique. The computational domain chosen is a simple channel with a biological type stenosis formed eccentrically on the top wall. The physiological pulsation is generated at the inlet using the first harmonic of the Fourier series of pressure pulse. In LES, the large scale flows are resolved fully while the unresolved subgrid scale (SGS) motions are modelled using a localized dynamic model. Due to the narrowing of artery the pulsatileflow becomes transition-to-turbulent in the downstream region of the stenosis, where a high level of turbulent fluctuations is achieved, and some detailed information about the nature of these fluctuations are revealed through the investigation of the turbulent energy spectra. Transition-to-turbulent of the pulsatileflow in the post stenosis is examined through the various numerical results such as velocity, streamlines, velocity vectors, vortices, wall pressure and shear stresses, turbulent kinetic energy, and pressure gradient. A comparison of the LES results with the coarse DNS are given for the Reynolds number of 2000 in terms of the mean pressure, wall shear stress as well as the turbulent characteristics. The results show that the shear stress at the upper wall is low just prior to the centre of the stenosis, while it is maximum in the throat of the stenosis. But, at the immediate post stenotic region, the wall shear stress takes the oscillating form which is quite harmful to the blood cells and vessels. In addition, the pressure drops at the throat of the stenosis where the re-circulated flow region is created due to the adverse pressure gradient. The maximum turbulent kinetic energy is located at the post stenosis with the presence of the inertial sub-range region of slope −5/3

Molecular Biomarkers of Response to PD-1/PD-L1 Immune Checkpoint Blockade in Advanced Bladder Cancer

Background: The activity of PD-1/PD-L1 inhibitors in the treatment of advanced bladder cancer (BC) is promising for many patients. However, a subset of patients do not benefit from treatment, thus leading to an effort to better identify predictive molecular biomarkers of response. Objective: To conduct a systematic review of the literature on predictive molecular biomarkers associated with response to PD-1 and PD-L1 inhibitors in advanced bladder cancer, defined as locally-advanced, unresectable, or metastatic (mBC) disease. Methods: A search of the literature was performed using Embase (1947 – January 2019), Medline (1946 – January 2019), and EBM Reviews for Cochrane Central Register of Controlled Trials (as of December 2018). Studies examining the association of molecular biomarkers with clinical outcome in BC treated with PD-1 or PD-L1 monotherapy were included. Outcomes of interest were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), duration of response, and objective response rate (ORR). Results: Using the study search criteria, 899 unique abstract citations were found, of which 834 did not meet the eligibility criteria. Full text of the remaining 65 citations were screened, and 50 studies excluded, including 18 review articles. Eight additional studies from the bibliography of the review papers were included, making a total of 23 studies. Five PD-1 / PD-L1 antibodies have been tested in BC immunohistochemistry (IHC). These studies used different expression scoring criteria and generally had poor ability to discriminate likelihood for response. Overall, the data suggests CD8+ T cell infiltration is necessary to mediate an antitumor immune response, but other immune cell populations, such as neutrophils may suppress T cell-mediated immunity and efficacy of PD-1/PD-L1 blockade. An IFN signature is a promising predictor, but there needs to be consensus on the optimal gene panel composition, and prospective validation. Tumor mutation burden (TMB) is a promising predictor in six studies reporting on 1200 patients, but there is not a consensus on the optimal definition of “high TMB”. Detection of T cell receptor (TCR) clonal expansion has only been conducted in small studies and so its predictive value remains inconclusive. Epithelial-mesenchymal transformation (EMT) and transforming growth factor (TGF) are associated with poor prognosis and possibly intrinsic resistance to PD-1/PD-L1 checkpoint blockade, but more work needs to be done to build upon and confirm the initial findings. Conclusions: Currently no molecular biomarker is sufficiently mature for routine clinical use, while some candidates, or a combination show great promise and need further study

The closest elastic tensor of arbitrary symmetry to an elasticity tensor of lower symmetry

The closest tensors of higher symmetry classes are derived in explicit form for a given elasticity tensor of arbitrary symmetry. The mathematical problem is to minimize the elastic length or distance between the given tensor and the closest elasticity tensor of the specified symmetry. Solutions are presented for three distance functions, with particular attention to the Riemannian and log-Euclidean distances. These yield solutions that are invariant under inversion, i.e., the same whether elastic stiffness or compliance are considered. The Frobenius distance function, which corresponds to common notions of Euclidean length, is not invariant although it is simple to apply using projection operators. A complete description of the Euclidean projection method is presented. The three metrics are considered at a level of detail far greater than heretofore, as we develop the general framework to best fit a given set of moduli onto higher elastic symmetries. The procedures for finding the closest elasticity tensor are illustrated by application to a set of 21 moduli with no underlying symmetry.Comment: 48 pages, 1 figur

Nonequilibrium phase transitions induced by multiplicative noise: effects of self-correlation

A recently introduced lattice model, describing an extended system which exhibits a reentrant (symmetry-breaking, second-order) noise-induced nonequilibrium phase transition, is studied under the assumption that the multiplicative noise leading to the transition is colored. Within an effective Markovian approximation and a mean-field scheme it is found that when the self-correlation time of the noise is different from zero, the transition is also reentrant with respect to the spatial coupling D. In other words, at variance with what one expects for equilibrium phase transitions, a large enough value of D favors disorder. Moreover, except for a small region in the parameter subspace determined by the noise intensity and D, an increase in the self-correlation time usually preventsthe formation of an ordered state. These effects are supported by numerical simulations.Comment: 15 pages. 9 figures. To appear in Phys.Rev.

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

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters