Therapeutic hypothermia after sudden cardiac arrest

Od niedawna metoda łagodnej hipotermii leczniczej jest uznawana za standardowe postępowanie, zaakceptowane przez amerykańskie i europejskie towarzystwa naukowe (Europejska Rada Resuscytacji, American Heart Association). W Klinice Kardiologii Uniwersytetu Medycznego w Lublinie od 2013 roku istnieje możliwość zastosowania hipotermii — zarówno zewnętrznej, jak i wewnątrznaczyniowej. W klinice rozpoczęto zbieranie własnych doświadczeń i zgłoszono ośrodek do zarejestrowania w Polskim Rejestrze Hipotermii Leczniczej. Z tego wynika zainteresowanie tematem i motywacja do napisania niniejszego opracowania. W 2012 roku, pod patronatem i z inicjatywy Sekcji Intensywnej Terapii i Resuscytacji Polskiego Towarzystwa Kardiologicznego oraz ówczesnego Krajowego Konsultanta ds. Kardiologii Profesora Grzegorza Opolskiego, powstał Polski Rejestr Hipotermii Leczniczej. Powołano również Radę Naukową Projektu. Zostały w nim zaproponowane standardowe procedury postępowania w celu ujednolicenia zasad leczenia chorych metodą hipotermii. W tym artykule omówiono wskazania i przeciwwskazania, możliwe powikłania i aspekty techniczne hipotermii.Mild therapeutic hypothermia has recently been recognized as standard procedure, accepted by American and European scientific societies (European Resuscitation Council, American Heart Association). In the Department of Cardiology at Medical University of Lublin we recently have possibility to use both invasive and non-invasive hypothermia. In the clinic began gathering our own experience and this center has been submitted for registration in Polish Register of Therapeutic Hypothermia, and that was the reason of our interest in the subject and motivation for the present study. The Polish Registry of Therapeutic Hypothermia came into 2012 year under the patronage of Section of Intensive Care and Resuscitation of Polish Cardiac Society and National Cardiac Consultant Professor Grzegorz Opolski. The Project Scientific Council has been created as well. Standard procedures have been proposed in order to standardize procedures used in treating patients with therapeutic hypothermia. The present study discusses indications and contraindications, possible complications and technical aspects of hypothermia

Cell-free synthesis of a functional G protein-coupled receptor complexed with nanometer scale bilayer discs

<p>Abstract</p> <p>Background</p> <p>G protein coupled receptors (GPCRs) represent the largest family of membrane proteins in the human genome and the richest source of targets for the pharmaceutical industry. A major limitation to characterizing GPCRs has been the difficulty in developing high-level heterologous expression systems that are cost effective. Reasons for these difficulties include inefficient transport and insertion in the plasma membrane and cytotoxicity. Additionally, GPCR purification requires detergents, which have a negative effect on receptor yields and stability.</p> <p>Results</p> <p>Here we report a detergent-free cell-free protein expression-based method to obtain pharmacologically active GPCRs in about 2 hours. Our strategy relies on the co-translational insertion of modified GPCRs into nanometer-sized planar membranes. As a model we employed an engineered β2-adrenergic receptor in which the third intracellular loop has been replaced with T4 lysozyme (β2AR -T4L). We demonstrated that nanolipoprotein particles (NLPs) are necessary for expression of active β2AR -T4L in cell-free systems. The binding specificity of the NLP- β2AR-T4L complex has been determined by competitive assays. Our results demonstrate that β2AR-T4L synthesized <it>in vitro </it>depends on similar oxidative conditions as those required by an <it>in vivo</it>-expressed receptor.</p> <p>Conclusions</p> <p>Although the activation of β2AR-T4L requires the insertion of the T4 lysozyme sequence and the yield of that active protein limited, our results conceptually prove that cell-free protein expression could be used as a fast approach to express these valuable and notoriously difficult-to-express proteins.</p

Gaussianity of Cosmic Velocity Fields and Linearity of the Velocity-Gravity Relation

We present a numerical study of the relation between the cosmic peculiar velocity field and the gravitational acceleration field. We show that on mildly non-linear scales (4-10 Mpc Gaussian smoothing), the distribution of the Cartesian coordinates of each of these fields is well approximated by a Gaussian. In particular, their kurtoses and negentropies are small compared to those of the velocity divergence and density fields. We find that at these scales the relation between the velocity and gravity field follows linear theory to good accuracy. Specifically, the systematic errors in velocity-velocity comparisons due to assuming the linear model do not exceed 6% in beta. To correct for them, we test various nonlinear estimators of velocity from density. We show that a slight modification of the alpha-formula proposed by Kudlicki et al. yields an estimator which is essentially unbiased and has a small variance.Comment: 11 pages, 15 figures; matches the version accepted for publication in MNRA

Evidence for a second phosphorylation site on eIF-2α from rabbit reticulocytes

AbstractSer 51 in the NH2-terminal sequence of the α-subunit of eukaryotic peptide initiation factor 2 (eIF-2) has been identified as a second phosphorylation site for the heme-controlled eIF-2α kinase from rabbit reticulocytes. Increased phosphorylation of this serine relative to the previously described phosphorylation site (Ser 48) is observed when the kinase reaction is carried out in the presence of the α-subunit of spectrin. A synthetic peptide corresponding to eIF-2α(41–54) is phosphorylated only in Ser 51 by the eIF-2α kinase

Reconstructing Cosmic Peculiar Velocities from the Mildly Nonlinear Density Field

We present a numerical study of the cosmic density vs. velocity divergence relation (DVDR) in the mildly non-linear regime. We approximate the dark matter as a non-relativistic pressureless fluid, and solve its equations of motion on a grid fixed in comoving coordinates. Unlike N-body schemes, this method yields directly the volume-averaged velocity field. The results of our simulations are compared with the predictions of the third-order perturbation theory (3PT) for the DVDR. We investigate both the mean `forward' relation (density in terms of velocity divergence) and the mean `inverse' relation (velocity divergence in terms of density), with emphasis on the latter. On scales larger than about 20 megaparsecs, our code recovers the predictions of 3PT remarkably well, significantly better than recent N-body simulations. On scales of a few megaparsecs, the DVDR predicted by 3PT differs slightly from the simulated one. In particular, approximating the inverse DVDR by a third-order polynomial turns out to be a poor fit. We propose a simple analytical description of the inverse relation, which works well for mildly non-linear scales.Comment: 9 pages, 7 figures (9 ps files), mn.st

The velocity-density relation in the spherical model

We study the cosmic velocity-density relation using the spherical collapse model (SCM) as a proxy to non-linear dynamics. Although the dependence of this relation on cosmological parameters is known to be weak, we retain the density parameter Omega_m in SCM equations, in order to study the limit Omega_m -> 0. We show that in this regime the considered relation is strictly linear, for arbitrary values of the density contrast, on the contrary to some claims in the literature. On the other hand, we confirm that for realistic values of Omega_m the exact relation in the SCM is well approximated by the classic formula of Bernardeau (1992), both for voids (delta<0) and for overdensities up to delta ~ 3. Inspired by this fact, we find further analytic approximations to the relation for the whole range delta from -1 to infinity. Our formula for voids accounts for the weak Omega_m-dependence of their maximal rate of expansion, which for Omega_m < 1 is slightly smaller that 3/2. For positive density contrasts, we find a simple relation div v = 3 H_0 (Omega_m)^(0.6) [ (1+delta)^(1/6) - (1+delta)^(1/2) ], that works very well up to the turn-around (i.e. up to delta ~ 13.5 for Omega_m = 0.25 and neglected Omega_Lambda). Having the same second-order expansion as the formula of Bernardeau, it can be regarded as an extension of the latter for higher density contrasts. Moreover, it gives a better fit to results of cosmological numerical simulations.Comment: 11 pages, 6 figures. Accepted for publication in MNRA