Molecular cytogenetic aberrations in patients with multiple myeloma studied by interphase fluorescence in situ hybridization

Background: Multiple myeloma (MM) is an incurable hematological disorder characterized by the accumulation of malignant plasma cells within the bone marrow (BM). The clinical heterogeneity of MM is dictated by the cytogenetic aberrations present in the clonal plasma cells (PCs). Cytogenetic studies in MM are hampered by the hypoproliferative nature of plasma cells in MM. Therefore, fluorescence in situ hybridization (FISH) analysis combined with magnetic-activated cell sorting (MACS) is an attractive alternative for evaluation of numerical and structural chromosomal changes in MM. Methods: Interphase FISH studies with three different specific probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV) and 1q12(CEP1 ) were performed in 48 MM patients. Interphase FISH studies with LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were used to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement. Results: Molecular cytogenetic aberrations were found in 40 (83.3%) of the 48 MM patients. 13 patients (27.1%) simultaneously had 13q deletion/monosomy 13 [del(13q14)], illegitimate IGH rearrangement and chromosome 1 abnormality. Del(13q14) was detected in 21 cases (43.7%), and illegitimate IGH rearrangements in 29 (60.4%) including 6 with t(11;14) and 5 with t(4;14). None of 9 patients with illegitimate IGH rearrangements and without t(11;14) or t(4;14) we detected had t(14;16) (q32;q23). 24 of the 48 MM patients (50%) had chromosome 1 abnormalities. Among 21 patients with del(13q14), 15 patients had Amp1q12;16 had IgH rearrangements. Whereas, among 27 cases without del(13q14), 8 had Amp1q12; 13 had IgH rearrangements. There was a strong association between del(13q14) and Amp1q12(c2 = 8.26, р < 0.01), and between del(13q14) and IgH rearrangement(c2 = 3.88, p < 0.05). Conclusion: 13q deletion/monosomy 13, IGH rearrangement and chromosome 1 abnormality are frequent in MM. They are not randomly distributed, but strongly interconnected. Interphase FISH technique combined with MACS using CD138-specific antibody is a highly sensitive technique at detecting molecular cytogenetic aberrations in MM.Обоснование: множественная миелома (MM) — неизлечимое гематологическое заболевание, характеризирующееся накоплением злокачественных плазматических клеток в костном мозге (КM). Клиническая гетерогенность MM определяется цитогенетическими аберрациями, присутствующими в клоне плазматических клеток (ПК). Цитогенетические исследования MM осложнены гипопролиферативными особенностями ПК. В связи с этим флуоресцентная гибридизация in situ (FISH) в комбинации с сортировкой клеток, активированных магнитными полями (MACS) представляется достойной альтернативой методам оценки точечных и структурных изменений хромосом при MM. Методы: интерфазные исследования методом FISH с использованием трех различных специфических зондов для участков, содержащих 13q14.3 (D13S319), 14q32 (IGHC/IGHV) и 1q12(CEP1), проводили у 48 больных с MM. Интерфазные исследования методом FISH с использованием зондов LSI IGH/CCND1, LSI IGH/FGFR3 и LSI IGH/MAF применяли для детекции t(11;14)(q13;q32), t(4;14)(p16;q32), и t(14;16)(q32;q23) у пациентов с перестройкой 14q32. Результаты: молекулярные цитогенетические аберрации выявляли у 40 (83,3%) из 48 больных с MM. У 13 пациентов (27,1%) одновременно определены 13q делеция/моносомия 13 [del(13q14)], аномальная перестройка IGH и аномалия хромосомы 1. Del(13q14) детектировали в 21 случае (43,7%), а аномальные перестройки IGH — в 29 (60,4%), в том числе у 6 пациентов с t(11;14) и 5 с t(4;14). Ни у одного из 9 больных с аномальными перестройками IGH и без t(11;14) или t(4;14) не выявляли транслокацию t(14;16) (q32;q23). У 24 из 48 пациентов с MM (50%) определяли аномалии хромосомы 1. В группе из 21 больных с del(13q14) в 15 случаях имелись перестройки IgH Amp1q12;16. В то же время из 27 случаев без del(13q14) у 8 содержались Amp1q12; в 13 случаях отмечали перестройки IgH. Выявлена взаимосвязь между del(13q14) и Amp1q12(χ2 = 8,26, p < 0,01) и между del(13q14) и перестройками IgH (χ2 = 3,88, p < 0,05). Выводы: 13q делецию/моносомию 13, перестройку IGH и аномалию хромосомы 1 часто отмечают при MM, причем их распределение не случайно и тесно взаимосвязано. Интерфазный анализ FISH в комбинации с MACS с использованием CD138-специфичных антител является высокочувствительным методом детекции молекулярных цитогенетических аберраций при MM

Discrete kink dynamics in hydrogen-bonded chains I: The one-component model

We study topological solitary waves (kinks and antikinks) in a nonlinear one-dimensional Klein-Gordon chain with the on-site potential of a double-Morse type. This chain is used to describe the collective proton dynamics in quasi-one-dimensional networks of hydrogen bonds, where the on-site potential plays role of the proton potential in the hydrogen bond. The system supports a rich variety of stationary kink solutions with different symmetry properties. We study the stability and bifurcation structure of all these stationary kink states. An exactly solvable model with a piecewise ``parabola-constant'' approximation of the double-Morse potential is suggested and studied analytically. The dependence of the Peierls-Nabarro potential on the system parameters is studied. Discrete travelling-wave solutions of a narrow permanent profile are shown to exist, depending on the anharmonicity of the Morse potential and the cooperativity of the hydrogen bond (the coupling constant of the interaction between nearest-neighbor protons).Comment: 12 pages, 20 figure

The Boltzmann equation without angular cutoff in the whole space: III, Qualitative properties of solutions

This is a continuation of our series of works for the inhomogeneous Boltzmann equation. We study qualitative properties of classical solutions, precisely, the full regularization in all variables, uniqueness, non-negativity and convergence rate to the equilibrium. Together with the results of Parts I and II about the well posedness of the Cauchy problem around Maxwellian, we conclude this series with a satisfactory mathematical theory for Boltzmann equation without angular cutoff

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb⁻¹ of pp collisions at \sqrts = 13 TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5). © 2019 The Author(s

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Search for long-lived neutral particles in pp collisions at s√=13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

This paper describes a search for pairs of neutral, long-lived particles decaying in the ATLAS calorimeter. Long-lived particles occur in many extensions to the Standard Model and may elude searches for new promptly decaying particles. The analysis considers neutral, long-lived scalars with masses between 5 and 400 GeV, produced from decays of heavy bosons with masses between 125 and 1000 GeV, where the long-lived scalars decay into Standard Model fermions. The analysis uses either 10.8 fb−1 or 33.0 fb−1 of data (depending on the trigger) recorded in 2016 at the LHC with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of 13 TeV. No significant excess is observed, and limits are reported on the production cross section times branching ratio as a function of the proper decay length of the long-lived particles