Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure

Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus,we aimed to examinewhether decreased expression of the rapid delayed rectifier potassiumcurrent, IKr, contributes to repolarization abnormalities in human HF. Tomap functional IKr expression across the left ventricle (LV), we optically imaged coronary-perfused LV free wall from donor and end-stage failing human hearts. The LV wedge preparation was used to examine transmural AP durations at 80% repolarization (APD80), and treatment with the IKr-blocking drug, E-4031, was utilized to interrogate functional expression. We assessed the percent change in APD80 post-IKr blockade relative to baseline APD80 (ΔAPD80) and found that ΔAPD80s are reduced in failing versus donor hearts in each transmural region, with 0.35-, 0.43-, and 0.41-fold reductions in endo-, mid-, and epicardium, respectively (p = 0.008, 0.037, and 0.022). We then assessed hERG1 isoform gene and protein expression levels using qPCR and Western blot. While we did not observe differences in hERG1a or hERG1b gene expression between donor and failing hearts, we found a shift in the hERG1a:hERG1b isoform stoichiometry at the protein level. Computer simulations were then conducted to assess IKr block under E-4031 influence in failing and nonfailing conditions. Our results confirmed the experimental observations and E-4031-induced relative APD80 prolongationwas greater in normal conditions than in failing conditions, provided that the cellularmodel of HF included a significant downregulation of IKr. In humanHF, the response to IKr blockade is reduced, suggesting decreased functional IKr expression. This attenuated functional response is associated with altered hERG1a:hERG1b protein stoichiometry in the failing human LV, and failing cardiomyoctye simulations support the experimental findings. Thus, of IKr protein and functional expression may be important determinants of repolarization remodeling in the failing human LV.We thank the Translational Cardiovascular Biobank & Repository (TCBR) at Washington University for provision of donor/patient records. The TCBR is supported by the NIH/CTSA (UL1 TR000448), Children's Discovery Institute, and Richard J. Wilkinson Trust. We also thank the laboratory of Dr. Sakiyama-Elbert for the use of the StepOnePlus equipment We appreciate the critical feedback on the manuscript by Dr. Jeanne Nerbonne. This work has been supported by the National Heart, Lung & Blood Institute (NHLBI, R01 HL114395). K. Holzem has been supported by the American Heart Association (12PRE12050315) and the NHLBI (F30 HL114310).Holzem, KM.; Gómez García, JF.; Glukhov, AV.; Madden, EJ.; Koppel, AC.; Ewald, GA.; Trénor Gomis, BA.... (2016). Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure. Journal of Molecular and Cellular Cardiology. 96:82-92. https://doi.org/10.1016/j.yjmcc.2015.06.008S82929

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Measurement of forward W→eνW\to e\nu production in pppp collisions at s=8 \sqrt{s}=8\,TeV

A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{align*} \begin{split} \sigma_{W^{+} \to e^{+}\nu_{e}}&=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb},\\ \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}&=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{split} \end{align*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{align*} \begin{split} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{split} \end{align*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{equation*} \sigma_{W^{+} \to e^{+}\nu_{e}}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb}, \end{equation*} \begin{equation*} \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{equation*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{equation*} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{equation*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for W → eν production in pp collisions is presented using data corresponding to an integrated luminosity of 2 fb$^{−1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8$ TeV. The electrons are required to have more than 20 GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive W production cross-sections, where the W decays to eν, are measured to be ${\sigma}_{W^{+}\to {e}^{+}{\nu}_e}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\kern0.5em \mathrm{p}\mathrm{b},$ ${\sigma}_{W^{-}\to {e}^{-}{\overline{\nu}}_e}=809.0\pm 1.9\pm 18.1\pm \kern0.5em 7.0\pm \kern0.5em 9.4\,\mathrm{p}\mathrm{b},$ where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination

First Data on the Age and Growth of Schmidt’s cod <i>Lepidion schmidti</i> (Moridae) from Waters of the Emperor Seamounts (Northwestern Pacific)

This study presents the first data of growth and age of Schmidt’s cod Lepidion schmidti, a rare and poorly studied member of the Moridae family (Gadiformes, Teleostei). The research was focused on the Emperor Seamounts area with the aim of investigating the age, growth rates, and longevity of this species. The analysis involved examining annual growth increments on sagittal otoliths. Data were taken from longline catches in 2014 and 2016, resulting in the collection of 140 individuals and the use of 70 otoliths for age determination. The results revealed that Schmidt’s cod can live for up to 49 years, with a mean age of 31.5 years in the catches. The relationship between body weight and total length was described by a power function, indicating positive allometric growth. The most suitable growth model for this species was determined to be the Von Bertalanffy growth equation. These results provide valuable insights to add to the limited knowledge of growth and age in the Moridae family and emphasize the long lifespan and slow growth of Schmidt’s cod

The theory of nonlinear systems as an instrument for solving engineering problems

The article outlines theoretical, methodological and practical issues of modern control and optimization theory, as well as the problems of nonlinear systems theory. Theoretical conclusions and results allowed to build mathematical models applicable to the management of objects of different nature with different principles of action, in particular, to the management of complex technical and technological objects that can be considered as nonlinear dynamic systems. The authors find it appropriate to consider nonlinear dynamic integral models as Volterra integro-power series from many functional arguments with multidimensional weight functions and a certain finite set of inputs to the system. The set of multidimensional kernels of integral Volterra operators completely characterizes the nonlinear and dynamic properties, and, consequently, the technical state of the initial system. The application of Volterra series based models allows to take into account the nonlinear and inertial properties of the initial nonlinear dynamic system more fully and accurately, it also makes the model diagnostic of a technical system more universal, raises the reliability of the forecast. The diagnostic procedure in this case is aimed at defining Volterra kernels based on the data of “input-output” experiment and building the diagnostic system of attribute in the space of which the decisive rule of optimal classification is created

The theory of nonlinear systems as an instrument for solving engineering problems

The article outlines theoretical, methodological and practical issues of modern control and optimization theory, as well as the problems of nonlinear systems theory. Theoretical conclusions and results allowed to build mathematical models applicable to the management of objects of different nature with different principles of action, in particular, to the management of complex technical and technological objects that can be considered as nonlinear dynamic systems. The authors find it appropriate to consider nonlinear dynamic integral models as Volterra integro-power series from many functional arguments with multidimensional weight functions and a certain finite set of inputs to the system. The set of multidimensional kernels of integral Volterra operators completely characterizes the nonlinear and dynamic properties, and, consequently, the technical state of the initial system. The application of Volterra series based models allows to take into account the nonlinear and inertial properties of the initial nonlinear dynamic system more fully and accurately, it also makes the model diagnostic of a technical system more universal, raises the reliability of the forecast. The diagnostic procedure in this case is aimed at defining Volterra kernels based on the data of “input-output” experiment and building the diagnostic system of attribute in the space of which the decisive rule of optimal classification is created

The Method of Forming the Recognition Signs Based on the Wavelet Transform of Radar Range Portraits

Рассматривается методика формирования высококонтрастных признаков в задаче радиолокационного распознавания с использованием вейвлет-преобразованияThe article considers the basic of forming high-contrasts features in the problem of radar recognition with wavelet transfor

Assessment of Prognostic Factors for Reconstruction of the Upper Third of the Ureter with A Tubularized Pelvis Flap

Ureteral plastic with a tubularized pelvic flap is a rare option of ureteral reconstruction. We present the assessment of the factors that are important for predicting the success of this operation.The aim. The purpose of the study was to assess the factors that are important in predicting the success of reconstruction of the upper third of the ureter with a tubularized pelvis flap.Material and methods. The study included 73 patients who were divided into 2 groups. The first group had extended strictures of the upper third of the ureter (n=14 / 19.2 %), and the second group had pathology of the ureteropelvic junction associated with ureterovascular conflict (n=59 / 80.8 %).Results. The length of the pelvic flap varied from 2.5 to 10.0 cm and reached an average of 3.9 cm. Early postoperative complications (Clavien-Dindo gradation &lt;3) were observed in 14 (9.2 %) patients out of 73, and dominated in the first group. The total number of positive long-term results (good + satisfactory) was 97.3 %. Two poor results were reported only in patients of the first group with prolonged recurrent strictures. A significant factor in the prognosis of complications was the secondary nature of the operation (p &lt;0.004). The factors of the long-term results prognosis were the performance of dismembered tubularized flap pyeloplasty due to the extended strictures of the upper third of the ureter, and the duration of the operation more than 120 minutes (p &lt;0.009 and p &lt;0.026).Conclusion. Surgical correction of the upper third of the ureter by a tubularized pelvis flap is a highly effective and safe method of reconstruction of the upper urinary tract. The main negative factors in the prognosis of this operation results are the secondary nature of the operation, the performance of the dismembered tubularized flap pyeloplasty because of the extended strictures of the upper third of the ureter, and the duration of the operation more than 120 minute

The Method of Forming the Recognition Signs Based on the Wavelet Transform of Radar Range Portraits

Рассматривается методика формирования высококонтрастных признаков в задаче радиолокационного распознавания с использованием вейвлет-преобразованияThe article considers the basic of forming high-contrasts features in the problem of radar recognition with wavelet transfor