A chemo-mechano-biological modeling framework for cartilage evolving in health, disease, injury, and treatment

Background and Objective:Osteoarthritis (OA) is a pervasive and debilitating disease, wherein degeneration of cartilage features prominently. Despite extensive research, we do not yet understand the cause or progression of OA. Studies show biochemical, mechanical, and biological factors affect cartilage health. Mechanical loads influence synthesis of biochemical constituents which build and/or break down cartilage, and which in turn affect mechanical loads. OA-associated biochemical profiles activate cellular activity that disrupts homeostasis. To understand the complex interplay among mechanical stimuli, biochemical signaling, and cartilage function requires integrating vast research on experimental mechanics and mechanobiology—a task approachable only with computational models. At present, mechanical models of cartilage generally lack chemo-biological effects, and biochemical models lack coupled mechanics, let alone interactions over time. Methods:We establish a first-of-its kind virtual cartilage: a modeling framework that considers time-dependent, chemo-mechano-biologically induced turnover of key constituents resulting from biochemical, mechanical, and/or biological activity. We include the “minimally essential” yet complex chemical and mechanobiological mechanisms. Our 3-D framework integrates a constitutive model for the mechanics of cartilage with a novel model of homeostatic adaptation by chondrocytes to pathological mechanical stimuli, and a new application of anisotropic growth (loss) to simulate degradation clinically observed as cartilage thinning. Results:Using a single set of representative parameters, our simulations of immobilizing and overloading successfully captured loss of cartilage quantified experimentally. Simulations of immobilizing, overloading, and injuring cartilage predicted dose-dependent recovery of cartilage when treated with suramin, a proposed therapeutic for OA. The modeling framework prompted us to add growth factors to the suramin treatment, which predicted even better recovery. Conclusions:Our flexible framework is a first step toward computational investigations of how cartilage and chondrocytes mechanically and biochemically evolve in degeneration of OA and respond to pharmacological therapies. Our framework will enable future studies to link physical activity and resulting mechanical stimuli to progression of OA and loss of cartilage function, facilitating new fundamental understanding of the complex progression of OA and elucidating new perspectives on causes, treatments, and possible preventions

Machine learning classification of OARSI-scored human articular cartilage using magnetic resonance imaging

SummaryObjectiveThe purpose of this study is to evaluate the ability of machine learning to discriminate between magnetic resonance images (MRI) of normal and pathological human articular cartilage obtained under standard clinical conditions.MethodAn approach to MRI classification of cartilage degradation is proposed using pattern recognition and multivariable regression in which image features from MRIs of histologically scored human articular cartilage plugs were computed using weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHRM). The WND-CHRM method was first applied to several clinically available MRI scan types to perform binary classification of normal and osteoarthritic osteochondral plugs based on the Osteoarthritis Research Society International (OARSI) histological system. In addition, the image features computed from WND-CHRM were used to develop a multiple linear least-squares regression model for classification and prediction of an OARSI score for each cartilage plug.ResultsThe binary classification of normal and osteoarthritic plugs yielded results of limited quality with accuracies between 36% and 70%. However, multiple linear least-squares regression successfully predicted OARSI scores and classified plugs with accuracies as high as 86%. The present results improve upon the previously-reported accuracy of classification using average MRI signal intensities and parameter values.ConclusionMRI features detected by WND-CHRM reflect cartilage degradation status as assessed by OARSI histologic grading. WND-CHRM is therefore of potential use in the clinical detection and grading of osteoarthritis

Observation of Orbitally Excited B_s Mesons

We report the first observation of two narrow resonances consistent with states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+, \bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1}) = 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Search for chargino-neutralino production in ppbar collisions at sqrt(s) = 1.96 TeV

We present the results of a search for associated production of the chargino and neutralino supersymmetric particles using up to 1.1 fb-1 of integrated luminosity collected by the CDF II experiment at the Tevatron ppbar collider at a center-of-mass energy of 1.96 TeV. The search is conducted by analyzing events with a large transverse momentum imbalance and either three charged leptons or two charged leptons of the same electric charge. The numbers of observed events are found to be consistent with standard model expectations. Upper limits on the production cross section are derived in different theoretical models. In one of these models a lower limit on the mass of the chargino is set at 129 GeV/c^2 at the 95% confidence level.Comment: To be submitted to Phys.Rev.Let

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Commissioning and performance of the CMS pixel tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published verion of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe pixel detector of the Compact Muon Solenoid experiment consists of three barrel layers and two disks for each endcap. The detector was installed in summer 2008, commissioned with charge injections, and operated in the 3.8 T magnetic field during cosmic ray data taking. This paper reports on the first running experience and presents results on the pixel tracker performance, which are found to be in line with the design specifications of this detector. The transverse impact parameter resolution measured in a sample of high momentum muons is 18 microns.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Alignment of the CMS silicon tracker during commissioning with cosmic rays

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS silicon tracker, consisting of 1440 silicon pixel and 15 148 silicon strip detector modules, has been aligned using more than three million cosmic ray charged particles, with additional information from optical surveys. The positions of the modules were determined with respect to cosmic ray trajectories to an average precision of 3–4 microns RMS in the barrel and 3–14 microns RMS in the endcap in the most sensitive coordinate. The results have been validated by several studies, including laser beam cross-checks, track fit self-consistency, track residuals in overlapping module regions, and track parameter resolution, and are compared with predictions obtained from simulation. Correlated systematic effects have been investigated. The track parameter resolutions obtained with this alignment are close to the design performance.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)