A predictive model of energy savings from top of rail friction control

In this paper the authors present a predictive model of train energy requirements due to the application of a top of rail friction modifier (TOR-FM) versus dry wheel / rail conditions. Using the VAMPIRE® Pro simulation package, train energy requirements are modeled for two sets of TOR-FM frictional conditions, one using full Kalker coefficients and the other by using a Kalker factor of 18%. Both scenarios use a top of rail saturated coefficient of friction of 0.35. Under both TOR-FM frictional conditions, train energy savings are shown for complete laps of the Transportation Technology Center Inc.’s (TTCI) Transit Test Track (TTT) loop, and also when isolating only the tangent section of the loop. However, the magnitude of energy savings varies greatly depending on the Kalker coefficient factor used, highlighting the need to model this relationship as accurately as possible. These simulation results are compared with data obtained from a field study, in which train energy savings of 5.3% (lap) and 7.8% (tangent) are shown due to the application of TOR-FM

ABCB1 Overexpression Is a key initiator of resistance to tyrosine kinase inhibitors in CML cell lines

The tyrosine kinase inhibitor (TKI) imatinib has resulted in excellent responses in the majority of Chronic Myeloid Leukaemia (CML) patients; however, resistance is observed in 20-30% of patients. More recently, resistance to the second generation TKIs, nilotinib and dasatinib, has also been observed albeit at a lower incidence. ABCB1 has previously been implicated in TKI export and its overexpression linked to TKI resistance. In this study the dynamics of nilotinib resistance was studied in CML cell lines with particular focus on ABCB1 expression levels during development of resistance. Results revealed ABCB1 overexpression is likely an important initiator of nilotinib resistance in vitro. ABCB1 overexpression was also observed in cell lines as an intermediate step during development of resistance to imatinib and dasatinib in vitro. We conclude that ABCB1 overexpression may provide an initial platform to facilitate development of additional mechanisms for resistance to TKIs. This provides a rationale for investigating this phenomenon in patients undergoing TKI therapy.Laura N. Eadie, Timothy P. Hughes, Deborah L. Whit

C5AC_5^A axial form factor from bubble chamber experiments

A careful reanalysis of both Argonne National Laboratory and Brookhaven National Laboratory data for weak single pion production is done. We consider deuteron nuclear effects and normalization (flux) uncertainties in both experiments. We demonstrate that these two sets of data are in good agreement. For the dipole parametrization of $C_5^A(Q^2)$, we obtain $C_5^A(0)=1.19\pm 0.08$, $M_A=0.94\pm 0.03$ GeV. As an application we present the discussion of the uncertainty of the neutral current 1$\pi^0$ production cross section, important for the T2K neutrino oscillation experiment.Comment: 16 pages, 8 figures, 2 table

A New Technique for Finding Needles in Haystacks: A Geometric Approach to Distinguishing Between a New Source and Random Fluctuations

We propose a new test statistic based on a score process for determining the statistical significance of a putative signal that may be a small perturbation to a noisy experimental background. We derive the reference distribution for this score test statistic; it has an elegant geometrical interpretation as well as broad applicability. We illustrate the technique in the context of a model problem from high-energy particle physics. Monte Carlo experimental results confirm that the score test results in a significantly improved rate of signal detection.Comment: 5 pages, 4 figure

Electromagnetic form factors of the nucleon: new fit and analysis of uncertainties

Electromagnetic form factors of proton and neutron, obtained from a new fit of data, are presented. The proton form factors are obtained from a simultaneous fit to the ratio $\mu_p G_{Ep}/G_{Mp}$ determined from polarization transfer measurements and to $ep$ elastic cross section data. Phenomenological two-photon exchange corrections are taken into account. The present fit for proton was performed in the kinematical region $Q^2\in (0,6)$ GeV$^2$. Both for protons and neutrons we use the latest available data. For all form factors the uncertainties and correlations of form factor parameters are investigated with the $\chi^2$ method.Comment: 18 pages, 12 figure

ABCC6 plays a significant role in the transport of nilotinib and dasatinib, and contributes to TKI resistance in vitro, in both cell lines and primary patient mononuclear cells

ATP Binding Cassette family efflux proteins ABCB1 and ABCG2 have previously been demonstrated to interact with Tyrosine Kinase Inhibitors (TKIs); however, evidence for the interaction of other potentially relevant drug transporters with TKIs is lacking. Through Taqman transporter array technology we assessed the impact of nilotinib on mRNA expression of ABC transporters, with ABCC6 identified as a transporter of interest. Additionally, increased expression of ABCC6 mRNA was observed during in vitro development of nilotinib resistance in BCR-ABL1-expressing cell lines. K562 cells exposed to gradually increasing concentrations of nilotinib (to 2 μM) expressed up to 57-fold higher levels of ABCC6 mRNA when compared with control cells (p = 0.002). Analogous results were observed in nilotinib resistant K562-Dox cells (up to 33-fold higher levels of ABCC6, p = 0.002). IC50 experiments were conducted on patient mononuclear cells in the absence and presence of three ABCC6 inhibitors: indomethacin, probenecid and pantoprazole. Results demonstrated that all three inhibitors significantly reduced nilotinib IC50 (p<0.001) indicating ABCC6 is likely involved in nilotinib transport. Cell line data confirmed these findings. Similar results were obtained for dasatinib, but not imatinib. Combined, these studies suggest that nilotinib and dasatinib are likely substrates of ABCC6 and to our knowledge, this is the first report of ABCC6 involvement in TKI transport. In addition, ABCC6 overexpression may also contribute to nilotinib and dasatinib resistance in vitro. With nilotinib and dasatinib now front line therapy options in the treatment of CML, concomitant administration of ABCC6 inhibitors may present an attractive option to enhance TKI efficacy.Laura N. Eadie, Phuong Dang, Jarrad M. Goyne, Timothy P. Hughes, Deborah L. Whit

Statistical Mechanics of the Quantum K-Satisfiability problem

We study the quantum version of the random $K$-Satisfiability problem in the presence of the external magnetic field $\Gamma$ applied in the transverse direction. We derive the replica-symmetric free energy functional within static approximation and the saddle-point equation for the order parameter: the distribution $P[h(m)]$ of functions of magnetizations. The order parameter is interpreted as the histogram of probability distributions of individual magnetizations. In the limit of zero temperature and small transverse fields, to leading order in $\Gamma$ magnetizations $m \approx 0$ become relevant in addition to purely classical values of $m \approx \pm 1$. Self-consistency equations for the order parameter are solved numerically using Quasi Monte Carlo method for K=3. It is shown that for an arbitrarily small $\Gamma$ quantum fluctuations destroy the phase transition present in the classical limit $\Gamma=0$, replacing it with a smooth crossover transition. The implications of this result with respect to the expected performance of quantum optimization algorithms via adiabatic evolution are discussed. The replica-symmetric solution of the classical random $K$-Satisfiability problem is briefly revisited. It is shown that the phase transition at T=0 predicted by the replica-symmetric theory is of continuous type with atypical critical exponents.Comment: 35 pages, 23 figures; changed abstract, improved discussion in the introduction, added references, corrected typo

Quantum homodyne tomography with a priori constraints

I present a novel algorithm for reconstructing the Wigner function from homodyne statistics. The proposed method, based on maximum-likelihood estimation, is capable of compensating for detection losses in a numerically stable way.Comment: 4 pages, REVTeX, 2 figure

Fitting Parton Distribution Data with Multiplicative Normalization Uncertainties

We consider the generic problem of performing a global fit to many independent data sets each with a different overall multiplicative normalization uncertainty. We show that the methods in common use to treat multiplicative uncertainties lead to systematic biases. We develop a method which is unbiased, based on a self--consistent iterative procedure. We demonstrate the use of this method by applying it to the determination of parton distribution functions with the NNPDF methodology, which uses a Monte Carlo method for uncertainty estimation.Comment: 33 pages, 5 figures: published versio

Recent AEM Case Study Examples of a Full Waveform Time-Domain System for Near-Surface and Groundwater Applications

Early time or high frequency airborne electromagnetic data (AEM) are desirable for shallow sounding or mapping of resistive areas but this poses difficulties due to a variety of issues, such as system bandwidth, system calibration and parasitic loop capacitance. In an effort to address this issue, a continued system design strategy, aimed at improving its early-channel VTEM data, has achieved fully calibrated, quantitative measurements closer to the transmitter current turn-off, while maintaining reasonably optimal deep penetration characteristics. The new design implementation, known as “Full Waveform” VTEM was previously described by Legault et al. (2012). This paper presents some case-study examples of a Full Waveform helicopter time-domain EM system for near-surface application