A Mathematical Model for Complete Morphological Regression in Primary Operable HER2-Positive Breast Cancer

Background. Breast cancer (BC) is distinguished with its biological tumour subtypes as luminal A, B, HER2-positive and triple-negative. The current clinical guidelines of the Russian Ministry of Health prescribe neoadjuvant targeted chemotherapy as combined treatment in the HER2-positive cancer subtype. An adequate model for treatment efficacy prediction in such patients had been missing to date.Aim. Development of a mathematical model and its computer realisation for complete morphological regression estimation in patients with primary operable HER2-positive breast cancer.Materials and methods. Statistically significant predictors were estimated with the treatment outcome data on 103 HER2- positive breast cancer cases with neoadjuvant targeted chemotherapy. A binary logistic regression model was developed to account for a dichotomous variable dependency on certain predictors.Results and discussion. Multivariate analysis laid out a mathematical model and software “Complete morphological regression estimation in primary operable EGFR-expressing breast cancer under neoadjuvant chemotherapy”. Our results attest that the program correctly automates a systematic estimation of complete morphological regression achieved prior to neoadjuvant targeted chemotherapy and is clinically justified for optimising treatment regimens in primary operable HER2-positive BC.Conclusion. The mathematical model and computer program developed estimate the rate of complete morphological regression achieved prior to neoadjuvant targeted chemotherapy with a high 92 % sensitivity, 97.33 % specificity and 93.21% accuracy

First πK\pi K atom lifetime and πK\pi K scattering length measurements

The results of a search for hydrogen-like atoms consisting of $\pi^{\mp}K^{\pm}$ mesons are presented. Evidence for $\pi K$ atom production by 24 GeV/c protons from CERN PS interacting with a nickel target has been seen in terms of characteristic $\pi K$ pairs from their breakup in the same target ($178 \pm 49$) and from Coulomb final state interaction ($653 \pm 42$). Using these results the analysis yields a first value for the $\pi K$ atom lifetime of $\tau=(2.5_{-1.8}^{+3.0})$ fs and a first model-independent measurement of the S-wave isospin-odd $\pi K$ scattering length $\left|a_0^-\right|=\frac{1}{3}\left|a_{1/2}-a_{3/2}\right|= \left(0.11_{-0.04}^{+0.09} \right)M_{\pi}^{-1}$ ($a_I$ for isospin $I$).Comment: 14 pages, 8 figure

Determination of ππ\pi\pi scattering lengths from measurement of π+π−\pi^+\pi^- atom lifetime

The DIRAC experiment at CERN has achieved a sizeable production of $\pi^+\pi^-$ atoms and has significantly improved the precision on its lifetime determination. From a sample of 21227 atomic pairs, a 4% measurement of the S-wave $\pi\pi$ scattering length difference $|a_0-a_2| = (.0.2533^{+0.0080}_{-0.0078}|_\mathrm{stat}.{}^{+0.0078}_{-0.0073}|_\mathrm{syst})M_{\pi^+}^{-1}$ has been attained, providing an important test of Chiral Perturbation Theory.Comment: 6 pages, 6 figure

Investigation of K+K−K^+K^- pairs in the effective mass region near 2mK2m_K

The DIRAC experiment at CERN investigated in the reaction $\rm{p}(24~\rm{GeV}/c) + Ni$ the particle pairs $K^+K^-, \pi^+ \pi^-$ and $p \bar{p}$ with relative momentum $Q$ in the pair system less than 100 MeV/c. Because of background influence studies, DIRAC explored three subsamples of $K^+K^-$ pairs, obtained by subtracting -- using time-of-flight (TOF) technique -- background from initial $Q$ distributions with $K^+K^-$ sample fractions more than 70\%, 50\% and 30\%. The corresponding pair distributions in $Q$ and in its longitudinal projection $Q_L$ were analyzed first in a Coulomb model, which takes into account only Coulomb final state interaction (FSI) and assuming point-like pair production. This Coulomb model analysis leads to a $K^+K^-$ yield increase of about four at $Q_L=0.5$ MeV/c compared to 100 MeV/c. In order to study contributions from strong interaction, a second more sophisticated model was applied, considering besides Coulomb FSI also strong FSI via the resonances $f_0(980)$ and $a_0(980)$ and a variable distance $r^*$ between the produced $K$ mesons. This analysis was based on three different parameter sets for the pair production. For the 70\% subsample and with best parameters, $3680\pm 370$ $K^+K^-$ pairs was found to be compared to $3900\pm 410$ $K^+K^-$ extracted by means of the Coulomb model. Knowing the efficiency of the TOF cut for background suppression, the total number of detected $K^+K^-$ pairs was evaluated to be around $40000\pm 10\%$, which agrees with the result from the 30\% subsample. The $K^+K^-$ pair number in the 50\% subsample differs from the two other values by about three standard deviations, confirming -- as discussed in the paper -- that experimental data in this subsample is less reliable

Detection of π+π−\pi^+\pi^-atoms with the DIRAC spectrometer at CERN

The goal of the DIRAC experiment at CERN is to measure with high precision the lifetime of the $\pi^+\pi^-$ atom ($A_{2\pi}$), which is of order $3\times10^{-15}$ s, and thus to determine the s-wave $\pi\pi$-scattering lengths difference $|a_{0}-a_{2}|$. $A_{2\pi}$ atoms are detected through the characteristic features of $\pi^+\pi^-$ pairs from the atom break-up (ionization) in the target. We report on a first high statistics atomic data sample obtained from p Ni interactions at 24 GeV/$c$ proton momentum and present the methods to separate the signal from the background.Comment: 19 pages, 12 figures, 1 tabl

DIRAC: A High Resolution Spectrometer for Pionium Detection

The DIRAC spectrometer has been commissioned at CERN with the aim of detecting $\pi^+ \pi^-$ atoms produced by a 24 GeV/$c$ high intensity proton beam in thin foil targets. A challenging apparatus is required to cope with the high interaction rates involved, the triggering of pion pairs with very low relative momentum, and the measurement of the latter with resolution around 0.6 MeV/$c$. The general characteristics of the apparatus are explained and each part is described in some detail. The main features of the trigger system, data-acquisition, monitoring and setup performances are also given.Comment: 49 pages, 37 figures. Figures 1, 2, 5 and 28 are removed because of size limitations imposed by hep-ex. They don't offer essential information. Latex class file 'elsart.cls' also provide

First measurement of the π+π−\pi^+\pi^- atom lifetime

The goal of the DIRAC experiment at CERN (PS212) is to measure the $\pi^+\pi^-$ atom lifetime with 10% precision. Such a measurement would yield a precision of 5% on the value of the $S$-wave $\pi\pi$ scattering lengths combination $|a_0-a_2|$. Based on part of the collected data we present a first result on the lifetime, $\tau=[2.91 ^{+0.49}_{-0.62}]\times 10^{-15}$ s, and discuss the major systematic errors. This lifetime corresponds to $|a_0-a_2|=0.264 ^{+0.033}_{-0.020} m_{\pi}^{-1}$.Comment: 18 pages, 6 figure

Columnar Liquid Crystals in Cylindrical Nanoconfinement

Axial orientation of discotic columnar liquid crystals in nanopores of inorganic templates, with the columns parallel to the axis of the nanochannels, is considered desirable for applications such as production of molecular wires. Here, we evaluate experimentally the role of the rigidity of the LC columns in achieving such orientation in nanopores where the planar anchoring (i.e., columns parallel to wall surface) is enforced. We studied the columnar phase of several discotic compounds with increasing column rigidity in the following order: dendronized carbazole, hexakis(hexyloxy)triphenylene (HAT6), a 1:1 HAT6-trinitrofluorenone (TNF) complex, and a helicene derivative. Using 2-D X-ray diffraction, AFM, grazing incidence diffraction, and polarized microscopy, we observed that the orientation of the columns changes from circular concentric to axial with increasing column rigidity. Additionally, when the rigidity is borderline, increasing pore diameter can change the configuration from axial back to circular. We derive expressions for distortion free energy that suggest that the orientation is determined by the competition between, on the one hand, the distortion energy of the 2-d lattice and the mismatch of its crystallographic facets with the curved pore wall in the axial orientation and, on the other hand, the bend energy of the columns in the circular configuration. Furthermore, the highly detailed AFM images of the core of the disclinations of strength +1 and +1/2 in the center of the pore reveal that the columns spiral down to the very center of the disclination and that there is no amorphous or misaligned region at the core, as suggested previously

Evidence for πK\pi K-atoms with DIRAC

We present evidence for the first observation of electromagnetically bound $\pi^\pm K^\mp$-pairs ($\pi K$-atoms) with the DIRAC experiment at the CERN-PS. The $\pi K$-atoms are produced by the 24 GeV/c proton beam in a thin Pt-target and the $\pi^\pm$ and $K^\mp$-mesons from the atom dissociation are analyzed in a two-arm magnetic spectrometer. The observed enhancement at low relative momentum corresponds to the production of 173 $\pm$ 54 $\pi K$-atoms. The mean life of $\pi K$-atoms is related to the s-wave $\pi K$-scattering lengths, the measurement of which is the goal of the experiment. From these first data we derive a lower limit for the mean life of 0.8 fs at 90% confidence level.Comment: 15 pages, 9 figure

Improved siRNA/shRNA Functionality by Mismatched Duplex

siRNA (small interfering RNA) and shRNA (small hairpin RNA) are powerful and commonly used tools in biomedical research. Currently, siRNAs are generally designed as two 21 nt strands of RNA that include a 19 nt completely complementary part and a 2 nt overhang. However, since the si/shRNAs use the endogenous miRNA machinery for gene silencing and the miRNAs are generally 22 nt in length and contain multiple internal mismatches, we tested if the functionality can be increased by designing the si/shRNAs to mimic a miRNA structure. We systematically investigated the effect of single or multiple mismatches introduced in the passenger strand at different positions on siRNA functionality. Mismatches at certain positions could significantly increase the functionality of siRNAs and also, in some cases decreased the unwanted passenger strand functionality. The same strategy could also be used to design shRNAs. Finally, we showed that both si and miRNA structured oligos (siRNA with or without mismatches in the passenger strand) can repress targets in all individual Ago containing cells, suggesting that the Ago proteins do not differentiate between si/miRNA-based structure for silencing activity