Leukotriene E4 elimination and metabolism in normal human subjects

Radiolabeled leukotriene (LT) E4 was infused into three healthy subjects in order to assess the production and elimination of sulfidopeptide leukotriene metabolites in urine. Three different radiolabeled tracers were employed, [14,15-3H]LTE4, [35S]LTE4, and [14C] LTE4 in five separate infusion studies. There was a rapid disappearance of radioactivity from the vascular compartment in an apparent two-phase process. The first elimination phase had an apparent half-life of approximately 7 min. Radioactivity quickly appeared in the urine with 10-16% eliminated during the first 2 h following intravenous infusion; 7%, 2-5 h; 4%, 5-8 h; 4%, 8-15 h; and 1.5%, 15-24 h from the [14C] LTE4 experiments. Unmetabolized LTE4 was the major radioactive component in the first urine collection, but at later times two more polar compounds predominated. After extensive purification by normal phase-solid phase extraction and reverse-phase high performance liquid chromatography, these compounds were characterized by UV spectroscopy, co-elution with synthetic standards, negative ion electron capture gas chromatography/mass spectrometry, and tandem mass spectrometry. The two major urinary metabolites were structurally determined to be 14-carboxy-hexanor-LTE3 and the conjugated tetraene, 16-carboxy-\u39413-tetranor-LTE4. Three other minor metabolites were detectable in the first urine collection only and were characterized by co-elution with synthetic standards as 16-carboxy-tetranor-LTE3, 18-carboxy-dinor-LTE4, and 20-carboxy-LTE4. \u3c9-Oxidation and subsequent \u3b2-oxidation from the methyl terminus appeared to be the major metabolic fate for sulfidopeptide leukotrienes in man. The accumulation of the 14-COOH-LTE3 and 16-COOH-\u39413-LTE4 may reflect a rate-limiting step in further oxidation of these compounds which places a conjugated triene or conjugated tetraene, respectively, two carbons removed from the CoA ester moiety. Also in the first urine collection there was another minor metabolite identified as N-acetyl-LTE4, however, no subsequent \u3b2-oxidation of this metabolite was observed. The major metabolites of LTE4 might be useful in assessing in vivo production of sulfidopeptide leukotrienes in humans

Noise-induced switching between vortex states with different polarization in classical two-dimensional easy-plane magnets

In the 2-dimensional anisotropic Heisenberg model with XY-symmetry there are non-planar vortices which exhibit a localized structure of the z-components of the spins around the vortex center. We study how thermal noise induces a transition of this structure from one polarization to the opposite one. We describe the vortex core by a discrete Hamiltonian and consider a stationary solution of the Fokker-Planck equation. We find a bimodal distribution function and calculate the transition rate using Langer's instanton theory (1969). The result is compared with Langevin dynamics simulations for the full many-spin model.Comment: 15 pages, 4 figures, Phys. Rev. B., in pres

Enhanced Out-of-plane Emission of K+ Mesons observed in Au+Au Collisions at 1 AGeV

The azimuthal angular distribution of K+ mesons has been measured in Au + Au collisions at 1 AGeV. In peripheral and semi-central collisions, K+ mesons preferentially are emitted perpendicular to the reaction plane. The strength of the azimuthal anisotropy of K+ emission is comparable to the one of pions. No in-plane flow was found for K+ mesons near projectile and target rapidity.Comment: Accepted for publication in Phys. Rev.Let

Handbook for Aboriginal Alcohol and Drug Work

The Handbook for Aboriginal Alcohol and Drug Work is a practical tool written for Aboriginal drug and alcohol workers, mental health workers and others working in this field. It offers a detailed look at alcohol and drug work from clinical, through to prevention, early intervention and harm reduction. This handbook is also likely to help people working to improve policy and those advocating for change. The idea for it came from workers all over Australia. They told us that they needed an easy to use handbook that can help them respond to the range of alcohol and drug issues they face every day. They also told us that such a book needs to take into account the complex challenges facing workers when helping clients, their families and, sometimes, whole communities

Encoding Newton’s Alchemical Library: Integrating Traditional Bibliographic and Modern Computational Methods

The Chymistry of Isaac Newton (http://chymistry.org) project team has digitized and encoded, following the TEI Guidelines, the complete corpus of Newton’s alchemical manuscripts, which total more than two thousand pages and over one million words. Newton cited more than five thousand published and unpublished works in these manuscripts; many of his annotations reference items in his own library, as he was an exceptionally dedicated reader of alchemical texts. Newton’s extensive citations and annotations provide a window into his alchemical research and practices, and serve as the basis for our authoritative bibliography of his alchemical sources. The bibliography is being developed as both a stand-alone reference work and an integrated resource with the alchemical manuscripts, providing additional context for Newton’s citations and florilegia. Once finished, the bibliography will provide complete, structured citations—which often would appear very abbreviated or incomplete in the manuscripts—that can be formatted to comply with modern bibliographic conventions and bibliographic management systems. Our bibliography will also link to digitized online versions of the source texts available through Early English Books Online, HathiTrust Digital Library, and other digital repositories. The citations include quasi-facsimile title page transcription, a technique used for bibliographic description of rare books, to enable richer forms of citation analysis. By analyzing the citations, we will be able to date Newton’s manuscripts, cluster manuscripts that cite the same or related sources, and, ultimately, generate network graphs that will reveal connections between the cited authors and texts and how they influence Newton’s own ideas and work

Right Ventricular Dysfunction following Acute Myocardial Infarction in the Absence of Pulmonary Hypertension in the Mouse

Background Cardiac remodelling after AMI is characterized by molecular and cellular mechanisms involving both the ischemic and non-ischemic myocardium. The extent of right ventricular (RV) dilatation and dysfunction and its relation to pulmonary hypertension (PH) following AMI are unknown. The aim of the current study was to evaluate changes in dimensions and function of the RV following acute myocardial infarction (AMI) involving the left ventricle (LV). Methods We assessed changes in RV dimensions and function 1 week following experimental AMI involving the LV free wall in 10 mice and assessed for LV and RV dimensions and function and for the presence and degree of PH. Results RV fractional area change and tricuspidal annular plane systolic excursion significantly declined by 33% (P = 0.021) and 28% (P = 0.001) respectively. Right ventricular systolic pressure measured invasively in the mouse was within the normal values and unchanged following AMI. Conclusion AMI involving the LV and sparing the RV induces a significant acute decline in RV systolic function in the absence of pulmonary hypertension in the mouse indicating that RV dysfunction developed independent of changes in RV afterload

Fabrication and characterization of linear diffusers based on concave micro lens arrays

Abstract: We present a new approach of beam homogenizing elements based on a statistical array of concave cylindrical microlens arrays. Those elements are used to diffuse light in only one direction and can be employed together with fly’s eye condensers to generate a uniform flat top line for high power coherent light sources. Conception, fabrication and characterization for such 1D diffusers are presented in this paper

Value of supplemental interventions to enhance the effectiveness of physical exercise during respiratory rehabilitation in COPD patients. A Systematic Review

BACKGROUND: There is a controversy about the additional benefit of various supplemental interventions used in clinical practice to further enhance the effectiveness of respiratory rehabilitation in patients with Chronic obstructive pulmonary disease (COPD). The aim of this research was to assess randomised controlled trials (RCTs) testing the additional benefit of supplemental interventions during respiratory rehabilitation in COPD patients. METHODS: Systematic review with literature searches in six electronic databases, extensive hand-searching and contacting of authors. Two reviewers selected independently eligible RCTs, rated the methodological quality and extracted the data, which were analyzed considering the minimal important difference of patient-important outcomes where possible. FINDINGS: We identified 20 RCTs whereof 18 provided sufficient data for analysis. The methodological quality was low and sample sizes were too small for most trials to produce meaningful results (median total sample size = 28). Data from five trials showed that supplemental oxygen during exercise did not have clinically meaningful effects on health-related quality of life while improvements of exercise capacity may be even larger for patients exercising on room air. RCTs of adding assisted ventilation, nutritional supplements or a number of anabolically acting drugs do not provide sufficient evidence for or against the use any of these supplemental interventions. INTERPRETATION: There is insufficient evidence for most supplemental interventions during respiratory rehabilitation to estimate their additional value, partly due to methodological shortcomings of included RCTs. Current data do not suggest benefit from supplemental oxygen during exercise, although the methodological quality of included trials limits conclusions. To appropriately assess any of the various supplemental interventions used in clinical practice, pragmatic trials on respiratory rehabilitation of COPD patients need to consider methodological aspects as well as appropriate sample sizes

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology