Mol-CycleGAN - a generative model for molecular optimization

Designing a molecule with desired properties is one of the biggest challenges in drug development, as it requires optimization of chemical compound structures with respect to many complex properties. To augment the compound design process we introduce Mol-CycleGAN - a CycleGAN-based model that generates optimized compounds with high structural similarity to the original ones. Namely, given a molecule our model generates a structurally similar one with an optimized value of the considered property. We evaluate the performance of the model on selected optimization objectives related to structural properties (presence of halogen groups, number of aromatic rings) and to a physicochemical property (penalized logP). In the task of optimization of penalized logP of drug-like molecules our model significantly outperforms previous results

A fundamental test of the Higgs Yukawa coupling at RHIC in A+A collisions

Searches for the intermediate boson, $W^{\pm}$, the heavy quantum of the Weak Interaction, via its semi-leptonic decay, $W\to e +\nu$, in the 1970's instead discovered unexpectedly large hadron production at high $p_T$, notably $\pi^0$, which provided a huge background of $e^{\pm}$ from internal and external conversions. Methods developed at the CERN ISR which led to the discovery of direct-single-$e^{\pm}$ in 1974, later determined to be from the semi-leptonic decay of charm which had not yet been discovered, were used by PHENIX at RHIC to make precision measurements of heavy quark production in p-p and Au+Au collisions, leading to the puzzle of apparent equal suppression of light and heavy quarks in the QGP. If the Higgs mechanism gives mass to gauge bosons but not to fermions, then a proposal that all 6 quarks are nearly massless in a QGP, which would resolve the puzzle, can not be excluded. This proposal can be tested with future measurements of heavy quark correlations in A+A collisionsComment: 12 pages, 16 figures, 26th Winter Workshop on Nuclear Dynamics, Ocho Rios, Jamaica WI, January 2-9, 2010. Corrected citation of 1974 direct single lepton discover

Mol-CycleGAN : a generative model for molecular optimization

During the drug design process, one must develop a molecule, which structure satisfies a number of physicochemical properties. To improve this process, we introduce Mol-CycleGAN – a CycleGAN-based model that generates compounds optimized for a selected property, while aiming to retain the already optimized ones. In the task of constrained optimization of penalized logP of drug-like molecules our model significantly outperforms previous results

A New Integer Linear Programming Formulation to the Inverse QSAR/QSPR for Acyclic Chemical Compounds Using Skeleton Trees

33rd International Conference on Industrial, Engineering and Other Applications of Applied Intelligent Systems, IEA/AIE 2020, Kitakyushu, Japan, September 22-25, 2020.Computer-aided drug design is one of important application areas of intelligent systems. Recently a novel method has been proposed for inverse QSAR/QSPR using both artificial neural networks (ANN) and mixed integer linear programming (MILP), where inverse QSAR/QSPR is a major approach for drug design. This method consists of two phases: In the first phase, a feature function f is defined so that each chemical compound G is converted into a vector f(G) of several descriptors of G, and a prediction function ψ is constructed with an ANN so that ψ(f(G)) takes a value nearly equal to a given chemical property π for many chemical compounds G in a data set. In the second phase, given a target value y∗ of the chemical property π , a chemical structure G∗ is inferred in the following way. An MILP M is formulated so that M admits a feasible solution (x∗, y∗) if and only if there exist vectors x∗, y∗ and a chemical compound G∗ such that ψ(x∗)=y∗ and f(G∗)=x∗. The method has been implemented for inferring acyclic chemical compounds. In this paper, we propose a new MILP for inferring acyclic chemical compounds by introducing a novel concept, skeleton tree, and conducted computational experiments. The results suggest that the proposed method outperforms the existing method when the diameter of graphs is up to around 6 to 8. For an instance for inferring acyclic chemical compounds with 38 non-hydrogen atoms from C, O and S and diameter 6, our method was 5×104 times faster

Modeling clonal hematopoiesis in umbilical cord blood cells by CRISPR/Cas9

To investigate clonal hematopoiesis associated gene mutations in vitro and to unravel the direct impact on the human stem and progenitor cell (HSPC) compartment, we targeted healthy, young hematopoietic progenitor cells, derived from umbilical cord blood samples, with CRISPR/Cas9 technology. Site-specific mutations were introduced in defined regions of DNMT3A, TET2, and ASXL1 in CD34(+) progenitor cells that were subsequently analyzed in short-term as well as long-term in vitro culture assays to assess self-renewal and differentiation capacities. Colony-forming unit (CFU) assays revealed enhanced self-renewal of TET2 mutated (TET2(mut)) cells, whereas ASXL1(mut) as well as DNMT3A(mut) cells did not reveal significant changes in short-term culture. Strikingly, enhanced colony formation could be detected in long-term culture experiments in all mutants, indicating increased self-renewal capacities. While we could also demonstrate preferential clonal expansion of distinct cell clones for all mutants, the clonal composition after long-term culture revealed a mutation-specific impact on HSPCs. Thus, by using primary umbilical cord blood cells, we were able to investigate epigenetic driver mutations without confounding factors like age or a complex mutational landscape, and our findings provide evidence for a direct impact of clonal hematopoiesis-associated mutations on self-renewal and clonal composition of human stem and progenitor cells

Search for Narrow Diphoton Resonances and for gamma-gamma+W/Z Signatures in p\bar p Collisions at sqrt(s)=1.8 TeV

We present results of searches for diphoton resonances produced both inclusively and also in association with a vector boson (W or Z) using 100 pb^{-1} of p\bar p collisions using the CDF detector. We set upper limits on the product of cross section times branching ratio for both p\bar p\to\gamma\gamma + X and p\bar p\to\gamma\gamma + W/Z. Comparing the inclusive production to the expectations from heavy sgoldstinos we derive limits on the supersymmetry-breaking scale sqrt{F} in the TeV range, depending on the sgoldstino mass and the choice of other parameters. Also, using a NLO prediction for the associated production of a Higgs boson with a W or Z boson, we set an upper limit on the branching ratio for H\to\gamma\gamma. Finally, we set a lower limit on the mass of a `bosophilic' Higgs boson (e.g. one which couples only to \gamma, W, and Z$ bosons with standard model couplings) of 82 GeV/c^2 at 95% confidence level.Comment: 30 pages, 11 figure

Measurement of the Strong Coupling Constant from Inclusive Jet Production at the Tevatron pˉp\bar pp Collider

We report a measurement of the strong coupling constant, $\alpha_s(M_Z)$, extracted from inclusive jet production in $p\bar{p}$ collisions at $\sqrt{s}=$1800 GeV. The QCD prediction for the evolution of $\alpha_s$ with jet transverse energy $E_T$ is tested over the range 40<$E_T$<450 GeV using $E_T$ for the renormalization scale. The data show good agreement with QCD in the region below 250 GeV. In the text we discuss the data-theory comparison in the region from 250 to 450 GeV. The value of $\alpha_s$ at the mass of the $Z^0$ boson averaged over the range 40<$E_T$<250 GeV is found to be $\alpha_s(M_{Z})= 0.1178 \pm 0.0001{(\rm stat)}^{+0.0081}_{-0.0095}{\rm (exp. syst)}$. The associated theoretical uncertainties are mainly due to the choice of renormalization scale (^{+6%}_{-4%}) and input parton distribution functions (5%).Comment: 7 pages, 3 figures, using RevTeX. Submitted to Physical Review Letter

Measurement of the ttˉproductioncrosssectionint\bar{t} production cross section in p\bar{p}collisionsat collisions at \sqrt{s}$ = 1.8 TeV

We update the measurement of the top production cross section using the CDF detector at the Fermilab Tevatron. This measurement uses $t\bar{t}$ decays to the final states $e+\nu$+jets and $\mu+\nu$+jets. We search for $b$ quarks from $t$ decays via secondary-vertex identification or the identification of semileptonic decays of the $b$ and cascade $c$ quarks. The background to the $t\bar{t}$ production is determined primarily through a Monte Carlo simulation. However, we calibrate the simulation and evaluate its uncertainty using several independent data samples. For a top mass of 175 $GeV/c^2$, we measure $\sigma_{t\bar{t}}=5.1 \pm 1.5$ pb and $\sigma_{t\bar{t}}=9.2 \pm 4.3$ pb using the secondary vertex and the lepton tagging algorithms, respectively. Finally, we combine these results with those from other $t\bar{t}$ decay channels and obtain $\sigma_{t\bar{t}} = 6.5^{+1.7}_{-1.4}$ pb.Comment: The manuscript consists of 130 pages, 35 figures and 42 tables in RevTex. The manuscript is submitted to Physical Review D. Fixed typo in author lis

Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions

We describe a measurement of the charge asymmetry of leptons from W boson decays in the rapidity range 0 enu, munu events from 110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The asymmetry data constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry predictions that use parton distribution functions obtained from previously published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur

Measurement of the Decay Amplitudes of B0 --> J/psi K* and B0s --> J/psi phi Decays

A full angular analysis has been performed for the pseudo-scalar to vector-vector decays, B0 --> J/psi K* and B_s --> J/psi phi, to determine the amplitudes for decays with parity-even longitudinal and transverse polarization and parity-odd transverse polarization. The measurements are based on 190 B0 candidates and 40 B_s candidates collected from a data set corresponding to 89 inverse pb of pbarp collisions at root(s) = 1.8 TeV at the Fermilab Tevatron. In both decays the decay amplitude for longitudinal polarization dominates and the parity-odd amplitude is found to be small.Comment: 7 pages, 3 figures, 1 tabl