Asymmetric properties of long-term and total heart rate variability

We report on two new physiological phenomena: the long-term and total heart rate asymmetry, which describe a significantly larger contribution of heart rate accelerations to long-term and total heart rate variability. In addition to the existing pair of indices, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text {SD1}}_{\rm d}, {\text {SD1}}_{\rm a},$$\end{document} which are based on partitioning short-term variance, we introduce two other pairs of descriptors based on partitioning long-term (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text {SD2}}_{\rm d}, {\text {SD2}}_{\rm a}$$\end{document}) and total (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text {SDNN}}_{\rm d}, {\text {SDNN}}_{\rm a}$$\end{document}) heart rate variability. The new asymmetric descriptors are used to analyze RR intervals time series derived from the 30-min ECG recordings of 241 healthy subjects resting in supine position. It is shown that both new types of asymmetry are present in 76% of the subjects. The new phenomena reported here are real physiological findings rather than artifacts of the method since they vanish after data shuffling

Effect of Cryogrinding on Chemical Stability of the Sparingly Water-Soluble Drug Furosemide

Purpose To investigate the effect of cryogrinding on chemical stability of the diuretic agent furosemide and its mixtures with selected excipients. Methods Furosemide was ground at liquid nitrogen temperature for 30, 60, 120 and 180 min. Mixtures of furosemide-PVP and furosemide-inulin (1:1) were milled under cryogenic conditions. Materials were analyzed by XRD, UPLC, MS and NMR. Results Upon increasing the milling time, a significant build-up of an unidentified impurity 1, probably the main degradation product, was noticed. Cogrinding of furosemide with PVP and inulin worsened chemical stabilization of the pharmaceutical. The main degradation product formed upon cryomilling was subsequently identified as 4-chloro-5-sulfamoylanthranilic acid (CSA). Based on some theoretical considerations involving specific milling conditions, the milling intensity and an expected specific milling dose have been calculated. Results indicate that cryogenic grinding is capable to initiate mechanically induced decomposition of furosemide.Conclusions Cryogenic grinding can activate and accelerate not only structural changes (solid state amorphization) but also chemical decomposition of pharmaceuticals. A cryogenic milling device should be considered as a chemical reactor, where under favourable conditions chemical reactions could be mechanically initiated

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Intrauterine deaths — an unsolved problem in Polish perinatology

Objectives: The Polish criteria for “intrauterine death” include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. Material and methods: An analysis using 142,662 births in the period between 2015–2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. Results: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. Conclusions: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often

Physics Performance Report for PANDA: Strong Interaction Studies with Antiprotons

To study fundamental questions of hadron and nuclear physics in interactions of antiprotons with nucleons and nuclei, the universal PANDA detector will be built. Gluonic excitations, the physics of strange and charm quarks and nucleon structure studies will be performed with unprecedented accuracy thereby allowing high-precision tests of the strong interaction. The proposed PANDA detector is a state-of-the art internal target detector at the HESR at FAIR allowing the detection and identification of neutral and charged particles generated within the relevant angular and energy range. This report presents a summary of the physics accessible at PANDA and what performance can be expected.Comment: 216 page

Technical Design Report for the: PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined.Comment: 189 pages, 225 figures, 41 table

Synthese von diarylierten Imidazol-Derivaten und Untersuchungen zur biologischen Aktivität

Das Ziel der vorliegenden Arbeit war die Synthese und biologische Untersuchung von diarylierten Imidazol-Derivaten. Das Augenmerk richtete sich einerseits auf die selektive Inhibition der Butyrylcholinesterase (BChE) und andererseits auf eine gefäßerweiternde Wirkung der Substanzen. Die Hemmung der Aktivität der Acetylcholin- und der Butyrylcholinesterase spielt eine tragende Rolle in der Alzheimer-Forschung wie auch der Therapie dieser Erkrankung. Es wird angenommen, dass beim manifesten Morbus Alzheimer die BChE großteils für den Abbau von Acetylcholin verantwortlich ist (Greig et al., 2005). Eine erhöhte BChE-Aktivität führt daher zu einem verminderten Acetylcholinspiegel, was wiederum zu einer Verschlechterung der kognitiven Funktionen und Aufmerksamkeitsdefiziten führt. Die selektive Inhibition der BChE führt zu einem Anstieg von ACh im synaptischen Spalt und zu einer Verbesserung der kognitiven Fähigkeiten (Greig et al., 2005). Im Rahmen dieser Dissertation wurden diarylierte Imidazol-Derivate entwickelt, welche eine selektiv inhibierende Wirkung auf die Butyrylcholinesterase im mikromolaren Bereich aufweisen. Basierend auf den erhaltenen Ergebnissen der ersten Substanzen erfolgte eine Strukturoptimierung. Als wirkungsstärkstes strukturoptimiertes Diarylimidazolderivat hat sich 5-(3-Ethylthiophenyl)-2-(3-thienyl)-1H-imidazol Hydrochlorid (96 x HCl) mit einem IC50-Wert auf die Butyrylcholinesterase (BChE) von 0,10 +/- 0,01 µmol/L herausgestellt. Zusätzlich wurde der potenteste BChE-Inhibitor, Verbindung 96 x HCl auf eine mögliche inhibierende Wirkung auf die Beta-Amyloid-Fibrillaggregation mittels Thioflavin-T-Assay untersucht. Es konnte bei dieser Verbindung eine Inhibition auf die Amyloid-Beta-Fibrillogenese mit einem IC50-Wert von 5,8 µmol/L gemessen werden. Man kann deshalb bei dieser Substanz von einem dualen Inhibitor sprechen. Der LogP-Wert von 96 x HCl liegt bei 2,3 und deutet auf eine mögliche Hirngängigkeit hin. Da cerebrovaskuläre Demenzen eng mit der Alzheimer-Erkrankung (Hunter et al., 2012) verknüpft sind, wurden jene Derivate, welche eine Inhibierung auf die BChE zeigten, auf eine vasodilatierende Wirkung an der glatten Muskulatur von Gefäßen des Meerschweinchens untersucht. Die Testung wurde an vier unterschiedlichen Organpräparaten durchgeführt. Hier war der Fokus insbesondere auf die Gefäße der Aorta und Arteria pulmonalis gerichtet. Auffallend bei dieser Substanzklasse war die starke Wirkung jener Substanzen auf die Gefäße, welche bereits eine starke Inhibierung der BChE zeigten. Im Rahmen dieser Arbeit konnte ermittelt werden, dass bei 2,4(5)-Diarylimidazolderivaten für die selektive inhibierende Wirkung an der BChE und die vasodilatierende Wirkung an der Aorta und Arteria pulmonalis folgende Strukturelemente am Molekül essenziell sind: An Position 2 des Imidazolkerns unsubstituierte Pi-elektronenreiche Aryle (Ring A) wie Phenyl- bzw. Heterocyclen mit einem Pi-Elektronen-Überschuss. An Position 4 des Imidazolkerns Phenyle (Ring B), welche in Position 3 (meta-) Substituenten mit Elektronendonorfähigkeiten tragen. Festgestellt wurde, dass Thioether-anstelle von Etherfunktionalitäten eine bessere Wirkung besitzen