Hemodynamic and inotropic effects of endothelin-1 in vivo

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Contradictory results have been reported with regard to its inotropic effects. This study examined the dose-dependent (500, 1000, 2500, 5000 and 10,000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effects of ET-1 in 53 open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation the myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/kg) decrease of the left ventricular systolic pressure (LVSP) and the mean aortic pressure (AoPmean) was followed by a dose-related rise of these pressures (LVSP: -1%, -1%, +8%, +16% vs. preinfusion values; AoPmean: -11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) the cardiac output (CO) was reduced (CO: -8%, -23%, -40%, -50%). After an initial vasodilatation ET-1 elevates the total peripheral resistance (TPR: -1%, +49%, +139%, +215%) dose-dependently. 10,000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output). Since the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged under ET-1, the isovolumic measurements do not indicate a positive inotropic effect of ET-1 in vivo in contrast to published results of in vitro experiments. It may be possible that a direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropic effect due to the coronary-constrictive effect of ET-1

Landscape of Manufacturing Process of ATMP Cell Therapy Products for Unmet Clinical Needs

Immune cell therapies have been studied in numerous clinical trials using Advanced Therapy Medicinal Products (ATMP) against a number of diseases having no or inadequate alternative therapies available, for example, various cancer types, cerebral stroke, cardiac infarction, severe autoimmune disorders, or chronic infections. Despite the enormous number of positive observation in ex vivo or animal studies, convincing results in clinical studies remain scanty. The chapter presents a survey and reveals that the manufacturing of immune cells especially for clinical trials is until today primarily performed using archaic, scarcely controlled, and incomparable processes and methods. A deeper characterization of ex vivo expanded immune cells is urgently needed not only on the level of a few receptors and ligands on the cell surface but also with respect to the ever-contained subtypes in an expanded immune cell population, the pattern of secreted effector molecules, and their amounts over time and influences from in vivo components on them

Real-time Monitoring of High-speed Spindle Operations Using Infrared Data Transmission

AbstractHigh-performance cutting is carried out with high cutting and feed speeds. Particularly, the use of heavy cutting tools (e.g. in planing machines), it is important to monitor the clamping and balance condition of the mounted tool, as well as the process forces. Therefore, a real-time monitoring system for high-speed operations based on the IrDA protocol was developed. It could be shown that infrared data transmission systems allow shorter reaction times compared to conventional wireless LAN applications. The presented monitoring system provides a reaction time of 7.14 ms at a bandwidth of 42.5 kHz and a data rate of 4.1 MBit/s

Ectomycorrhizal influence on the dynamics of sesquiterpene release by Tricholoma vaccinum

Tricholoma vaccinum is an ectomycorrhizal basidiomycete with high host specificity. The slow-growing fungus is able to produce twenty sesquiterpenes, including α-barbatene, sativene, isocaryophyllene, α-cuprenene, β-cedrene, ß-copaene, 4-epi-α-acoradiene, and chamigrene in axenic culture. For the three major compounds, Δ(6)-protoilludene, β-barbatene, and an unidentified oxygenated sesquiterpene (m/z 218.18), changed production during co-cultivation with the ectomycorrhizal partner tree, Picea abies, could be shown with distinct dynamics. During the mycorrhizal growth of T. vaccinum–P. abies, Δ(6)-protoilludene and the oxygenated sesquiterpene appeared at similar times, which warranted further studies of potential biosynthesis genes. In silico analyses identified a putative protoilludene synthesis gene, pie1, as being up-regulated in the mycorrhizal stage, in addition to the previously identified, co-regulated geosmin synthase, ges1. We therefore hypothesize that the sesquiterpene synthase pie1 has an important role during mycorrhization, through Δ(6)-protoilludene and/or its accompanied oxygenated sesquiterpene production

Evaluating the accuracy of two: In situ optical sensors to estimate DOC concentrations for drinking water production

Two in situ optical sensors, a single-excitation fluorescence-based sensor (fDOM) mounted on a multi-parameter EXO2 sonde (YSI), and a stand-alone, multispectral absorbance-based instrument (spectro::lyser, scan Messtechnik GmbH), were evaluated for their capability to (i) estimate river dissolved organic carbon (DOC) concentrations and (ii) provide oversight of drinking water production. The sensors were deployed between March and November 2017 in the river Fyris, which drains a mixed forested and agricultural 2003 km$^{2}$ catchment and serves as a drinking water source by managed aquifer recharge. Grab samples were collected every 2 to 3 weeks and compared with logged sensor data collected at 15 minute intervals. The fDOM probe signal was used to estimate DOC concentrations in the range of 10.4 to 24.4 mg L$^{-1}$ using linear regression (R$^{2}$ = 0.71, RMSE = 2.5 mg L$^{-1}$), after correction for temperature, turbidity and inner-filter effects. Temporal changes in DOC character associated with the mixed land use landscape, as indicated by optical indices, reduced this sensor accuracy for estimating DOC concentration. Nevertheless, humic substance concentrations, the fraction of DOC that is preferentially removed during artificial infiltration, were well captured. The spectrolyser signal was used to establish a 2-component partial least square model that captured DOC fluctuations from 10.2 to 29.4 mg L$^{-1}$ (R$^{2}$ = 0.92; RMSE = 1.3 mg L$^{-1}$). This multiple-wavelength model (220 to 720 nm) effectively handled the changes in DOC composition while accurately estimating DOC concentrations. This study explores the advantages and limitations of optical sensors for their use in managed aquifer recharge and drinking water production in relation to DOC levels

Star Formation Activity in the Galactic HII Complex S255-S257

We present results on the star-formation activity of an optically obscured region containing an embedded cluster (S255-IR) and molecular gas between two evolved HII regions S255 and S257. We have studied the complex using optical, near-infrared (NIR) imaging, optical spectroscopy and radio continnum mapping at 15 GHz, along with Spitzer-IRAC results. It is found that the main exciting sources of the evolved HII regions S255 and S257 and the compact HII regions associated with S255-IR are of O9.5 - B3 V nature, consistent with previous observations. Our NIR observations reveal 109 likely young stellar object (YSO) candidates in an area of ~ 4'.9 x 4'.9 centered on S255-IR, which include 69 new YSO candidates. Our observations increased the number of previously identified YSOs in this region by 32%. To see the global star formation, we constructed the V-I/V diagram for 51 optically identified IRAC YSOs in an area of ~ 13' x 13' centered on S255-IR. We suggest that these YSOs have an approximate age between 0.1 - 4 Myr, indicating a non-coeval star formation. Using spectral energy distribution models, we constrained physical properties and evolutionary status of 31 and 16 YSO candidates outside and inside the gas ridge, respectively. The models suggest that the sources associated within the gas ridge are of younger population (mean age ~ 1.2 Myr) than the sources outside the gas ridge (mean age ~ 2.5 Myr). The positions of the young sources inside the gas ridge at the interface of the HII regions S255 and S257, favor a site of induced star formation.Comment: 46 pages, 14 figures, 5 tables. Accepted for publication in The Astrophysical Journa

The Role of Aerobic Physical Fitness in Overweight Adolescents

Photograph of H. and J. Shaw's Lang Wheels Jets J10 Centre Truck taken at Forest site, 29 September 1958 whole side view