First exploratory calculation of the long-distance contributions to the rare kaon decays <i>K</i> →π ℓ⁺ℓ^-

The rare decays of a kaon into a pion and a charged lepton/antilepton pair proceed via a flavour changing neutral current and therefore may only be induced beyond tree level in the Standard Model. This natural suppression makes these decays sensitive to the effects of potential New Physics. The CP conserving $K\to\pi \ell^+\ell^-$ decay channels however are dominated by a single photon exchange; this involves a sizeable long-distance hadronic contribution which represents the current major source of theoretical uncertainty. Here we outline our methodology for the computation of the long-distance contributions to these rare decay amplitudes using lattice QCD and present the numerical results of the first exploratory studies of these decays in which all but the disconnected diagrams are evaluated. The domain wall fermion ensembles of the RBC and UKQCD collaborations are used, with a pion mass of $M_{\pi}\sim 430\,\mathrm{MeV}$ and a kaon mass of $M_{K}\sim 625\,\mathrm{MeV}$. In particular we determine the form factor, $V(z)$, of the $K^+\to\pi^+\ell^+\ell^-$ decay from the lattice at small values of $z=q^2/M_{K}^{2}$, obtaining $V(z)=1.37(36),\, 0.68(39),\, 0.96(64)$ for the three values of $z=-0.5594(12),\, -1.0530(34),\, -1.4653(82)$ respectively.Comment: 40 pages, 14 figures, 4 table

Universal Fluctuations of the Danube Water Level: a Link with Turbulence, Criticality and Company Growth

A global quantity, regardless of its precise nature, will often fluctuate according to a Gaussian limit distribution. However, in highly correlated systems, other limit distributions are possible. We have previously calculated one such distribution and have argued that this function should apply specifically, and in many instances, to global quantities that define a steady state. Here we demonstrate, for the first time, the relevance of this prediction to natural phenomena. The river level fluctuations of the Danube are observed to obey our prediction, which immediately establishes a generic statistical connection between turbulence, criticality and company growth statistics.Comment: 5 pages, 1 figur

Exploratory lattice QCD study of the rare kaon decay K+→π+ννˉK^+\to\pi^+\nu\bar{\nu}

In Ref [1] we have presented the results of an exploratory lattice QCD computation of the long-distance contribution to the $K^+\to\pi^+\nu\bar{\nu}$ decay amplitude. In the present paper we describe the details of this calculation, which includes the implementation of a number of novel techniques. The $K^+\to\pi^+\nu\bar{\nu}$ decay amplitude is dominated by short-distance contributions which can be computed in perturbation theory with the only required non-perturbative input being the relatively well-known form factors of semileptonic kaon decays. The long-distance contributions, which are the target of this work, are expected to be of O(5%) in the branching ratio. Our study demonstrates the feasibility of lattice QCD computations of the $K^+\to\pi^+\nu\bar{\nu}$ decay amplitude, and in particular of the long-distance component. Though this calculation is performed on a small lattice ($16^3\times32$) and at unphysical pion, kaon and charm quark masses, $m_\pi=420$ MeV, $m_K=563$ MeV and m_c^{\overline{\mathrm{MS}}}(\mbox{2 GeV})=863 MeV, the techniques presented in this work can readily be applied to a future realistic calculation.Comment: 74 pages, 12 figure

Structure-guided machine learning prediction of drug resistance mutations in Abelson 1 kinase.

Funder: State Government of VictoriaKinases play crucial roles in cellular signalling and biological processes with their dysregulation associated with diseases, including cancers. Kinase inhibitors, most notably those targeting ABeLson 1 (ABL1) kinase in chronic myeloid leukemia, have had a significant impact on cancer survival, yet emergence of resistance mutations can reduce their effectiveness, leading to therapeutic failure. Limited effort, however, has been devoted to developing tools to accurately identify ABL1 resistance mutations, as well as providing insights into their molecular mechanisms. Here we investigated the structural basis of ABL1 mutations modulating binding affinity of eight FDA-approved drugs. We found mutations impair affinity of type I and type II inhibitors differently and used this insight to developed a novel web-based diagnostic tool, SUSPECT-ABL, to pre-emptively predict resistance profiles and binding free-energy changes (ΔΔG) of all possible ABL1 mutations against inhibitors with different binding modes. Resistance mutations in ABL1 were successfully identified, achieving a Matthew's Correlation Coefficient of up to 0.73 and the resulting change in ligand binding affinity with a Pearson's correlation of up to 0.77, with performances consistent across non-redundant blind tests. Through an in silico saturation mutagenesis, our tool has identified possibly emerging resistance mutations, which offers opportunities for in vivo experimental validation. We believe SUSPECT-ABL will be an important tool not just for improving precision medicine efforts, but for facilitating the development of next-generation inhibitors that are less prone to resistance. We have made our tool freely available at http://biosig.unimelb.edu.au/suspect_abl/

Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma

PLAUR polymorphisms and levels are associated with markers of airway remodelling in lung biopsies of asthma patients http://ow.ly/X5Sr

Domain wall QCD with physical quark masses

We present results for several light hadronic quantities ($f_\pi$, $f_K$, $B_K$, $m_{ud}$, $m_s$, $t_0^{1/2}$, $w_0$) obtained from simulations of 2+1 flavor domain wall lattice QCD with large physical volumes and nearly-physical pion masses at two lattice spacings. We perform a short, O(3)%, extrapolation in pion mass to the physical values by combining our new data in a simultaneous chiral/continuum `global fit' with a number of other ensembles with heavier pion masses. We use the physical values of $m_\pi$, $m_K$ and $m_\Omega$ to determine the two quark masses and the scale - all other quantities are outputs from our simulations. We obtain results with sub-percent statistical errors and negligible chiral and finite-volume systematics for these light hadronic quantities, including: $f_\pi$ = 130.2(9) MeV; $f_K$ = 155.5(8) MeV; the average up/down quark mass and strange quark mass in the $\bar {\rm MS}$ scheme at 3 GeV, 2.997(49) and 81.64(1.17) MeV respectively; and the neutral kaon mixing parameter, $B_K$, in the RGI scheme, 0.750(15) and the $\bar{\rm MS}$ scheme at 3 GeV, 0.530(11).Comment: 131 pages, 30 figures. Updated to match published versio

Prospects for a lattice computation of rare kaon decay amplitudes: K →π ℓ+ℓ- decays

The rare kaon decays $K\to\pi\ell^+\ell^-$ and $K\to\pi\nu\bar{\nu}$ are flavor changing neutral current (FCNC) processes and hence promising channels with which to probe the limits of the standard model and to look for signs of new physics. In this paper we demonstrate the feasibility of lattice calculations of $K\to\pi\ell^+\ell^-$ decay amplitudes for which long-distance contributions are very significant. We show that the dominant finite-volume corrections (those decreasing as powers of the volume) are negligibly small and that, in the four-flavor theory, no new ultraviolet divergences appear as the electromagnetic current $J$ and the effective weak Hamiltonian $H_W$ approach each other. In addition, we demonstrate that one can remove the unphysical terms which grow exponentially with the range of the integration over the time separation between $J$ and $H_W$. We will now proceed to exploratory numerical studies with the aim of motivating further experimental measurements of these decays. Our work extends the earlier study by Isidori, Turchetti and Martinelli which focussed largely on the renormalization of ultraviolet divergences. In a companion paper we discuss the evaluation of the long-distance contributions to $K\to\pi\nu\bar{\nu}$ decays; these contributions are expected to be at the level of a few percent for $K^+$ decays.Comment: Version published in Phys. Rev.

Prospects for a lattice computation of rare kaon decay amplitudes. II. K →π ν ν ¯ decays

The rare kaon decays $K\to\pi\nu\bar{\nu}$ are strongly suppressed in the standard model and widely regarded as processes in which new phenomena, not predicted by the standard model, may be observed. Recognizing such new phenomena requires precise standard model prediction for the braching ratio of $K\to\pi\nu\bar{\nu}$ with controlled uncertainty for both short-distance and long-distance contributions. In this work we demonstrate the feasibility of lattice QCD calculation of the long-distance contribution to rare kaon decays with the emphasis on $K^+\to\pi^+\nu\bar{\nu}$. Our methodology covers the calculation of both $W$-$W$ and $Z$-exchange diagrams. We discuss the estimation of the power-law, finite-volume corrections and two methods to consistently combine the long distance contribution determined by the lattice methods outlined here with the short distance parts that can be reliably determined using perturbation theory. It is a subsequent work of our first methodology paper on $K\to\pi\ell^+\ell^-$, where the focus was made on the $\gamma$-exchange diagrams.Comment: 47 pages, 5 figure