•Fuel can be used as heat sink for future aircraft propulsion concepts in multiple ways.•Active fuel circulation underneath exposed surfaces enables steady state cooling.•Cooling demands of a hybrid ...electric aircraft with peak heat loads of 120 kW are met.•On ground taxiing with low quantities of fuel left is the most challenging condition.•Removed aircraft drag increment caused by the thermal management system.
Fuel is assessed as alternative heat sink for future aircraft applications to avoid excessive drag from conventional cooling systems. Two cooling concepts using fuel as a heat sink are investigated for a hybrid electric aircraft platform with entry into service of year 2035+, 180 PAX and a design range of 1300 nm. The hybrid electric propulsion system produces a maximum heat power of 126.1 kW. Concept 1 uses active hot fuel circulation underneath the wing surfaces for cooling, whereas Concept 2 uses heat exchangers placed inside the existing tanks. Concept 1 is subdivided based on the fuel flow architecture into series and parallel configuration. Thermodynamic modeling is based on semi empirical methods combining effects of internal and external convection, conduction and radiation to an overall heat transfer model. A partial dependence analysis is performed to ensure the model's integrity. The cooling power potential of both concepts is evaluated at five mission points for the reference aircraft. Concept 1 provides sufficient cooling power for all operating points within the operational limits of the fuel temperature except for the Taxi case, in which the required cooling power is 85% fulfilled. The series and parallel sub configurations of Concept 1 are capable of equal cooling powers in all operating points. The parallel option requires less than half the hydraulic power of the series option. The final system needs a pump providing 2.3 kW of hydraulic power. Concept 2 fails to provide the required cooling power at any mission point other than Take-Off due to low fuel fill levels. Concept 1 is compared to a reference cooling system using a ram air cooler on aircraft level. A mass and drag sensitivity assessment shows that Concept 1 performance is in the range of 0.0% to +0.6% in fuel burn compared to the ram air cooling system depending on the mass considerations for Concept 1.
Dopamine is a catecholamine that serves as a neurotransmitter in the central and peripheral nervous system. Non‐invasive, reliable, and high‐throughput techniques for its quantification are needed to ...assess dysfunctions of the dopaminergic system and monitor therapies. We developed and validated a competitive ELISA for direct determination of dopamine in urine samples. The method provides high specificity, good accuracy, and precision (average inter‐assay variation < 12%). The analysis is not affected by general urinary components and structurally related drugs and metabolites. The correlation between ELISA and LC‐MS/MS analyses was very good (r = 0.986, n = 28). The reference range was 64–261 μg/g Cr (n = 64). Week‐to‐week biological variations of second morning urinary dopamine under free‐living conditions were 23.9% for within‐ and 35.5% for between‐subject variation (n = 10). The assay is applied in monitoring Parkinson's disease patients under different treatments. Urinary dopamine levels significantly increase in a dose‐dependent manner for Parkinson's disease patients under l‐DOPA treatment. The present ELISA provides a cost‐effective alternative to chromatographic methods to monitor patients receiving dopamine restoring treatment to ensure appropriate dosing and clinical efficacy. The method can be used in pathological research for the assessment of possible peripheral biological markers for disorders related to the dopaminergic system.
Our competitive ELISA for direct dopamine quantification in urine samples is a viable cost‐effective alternative to chromatographic analysis. The method is robust, sensitive, and very specific and it does not require sample pre‐treatment. It can be used in monitoring dopamine‐modulating therapies. Urinary dopamine levels significantly increase in a dose‐dependent manner for Parkinson's disease patients under l‐DOPA treatment.
Abstract Objective The effects of psychological stress, oxidative stress, and chronic low grade inflammation on the neuro-immune connection have been implicated in the pathogenesis of depression. ...Thus, in the recent past, there has been a growing effort in determining the mechanism of this pathogenesis. While attempting to map out, this mechanism researchers and clinicians have searched for clinically relevant biomarkers for use in the diagnosis and for the assessment of those suffering from depression. In this study, we have performed a retrospective analysis of biomarkers with clinically relevant potentials, including peripheral catecholamines, chemokines, cytokines, and neurotransmitters. Methods The retrospective analysis was performed on data collected over a six-year period of time (July 2009 to July 2015), gathered from patients ( N = 1399; M age = 42, SD = 13; 71% female, 29% male) who submitted samples with complaints of feeling hopeless, worthless, isolated, alone, general sadness, overwhelmed, and/or a lack of interest in things they once enjoyed. The data collected consisted of quantitative values of urinary catecholamines and neurotransmitters (peripheral dopamine, epinephrine, histamine, kynurenic acid, norepinephrine, β-PEA, and serotonin), salivary hormones (peripheral cortisol and melatonin), and peripheral blood mononuclear cell secreted cytokines and chemokines (Interleukins 1β, 6, 8, 10, MCP-1, GCSF, and TNFα). Statistical and clinical significance was assessed by comparison with a control group ( N = 2395; M age = 42, SD = 13; 70% female, 30% male), calculating the percent mean difference, p value, and effect size (Cohen's ɗ) for each parameter between groups. Results The findings of this study suggested that, in a model of general depression, there is a dysregulation in the enzymatic production and degradation of catecholamines, neurotransmitters, hormones, and immunological proteins. A cycle of interaction was found between all of these biomolecules, where an increase or decrease in one marker could result in a stimulatory or inhibitory effect on others. The mechanism of this was proposed to occur through the interaction of psychological stress, inflammation, and oxidative stress pathways. All of these biomolecules were found to be significantly altered in the general depression group and are key components of the interaction between the neurological and immunological systems. Conclusions This study serves to further elucidate the role of biomolecules in the regulation of affective disorders, such as depression. Resulting in providing a network of clinically relevant biomarkers to objectively assess and monitor general depression.
Abstract Background Pediatric obstructive sleep apnea (OSA) is associated with cognitive dysfunction, suggesting altered neurotransmitter function. We explored overnight changes in neurotransmitters ...in the urine of children with and without OSA. Methods Urine samples were collected from children with OSA and from control subjects before and after sleep studies. A neurocognitive battery assessing general cognitive ability (GCA) was administered to a subset of children with OSA. Samples were subjected to multiple enzyme-linked immunosorbent assays for 12 neurotransmitters, and adjusted for creatinine concentrations. Results The study comprised 50 children with OSA and 20 control subjects. Of the children with OSA, 20 had normal GCA score (mean ± SD) (101.2 ± 14.5) and 16 had a reduced GCA score (87.3 ± 13.9; P < .001). Overnight increases in epinephrine, norepinephrine, and γ-aminobutyric acid (GABA) levels emerged in children with OSA; taurine levels decreased. Using combinatorial approaches and cutoff values for overnight changes of these four neurotransmitters enabled prediction of OSA (area under the curve AUC: 0.923; P < .0001). Furthermore, GABA and taurine alterations, as well as overnight reductions in phenylethylamine, were more prominent in children with OSA and low GCA than in children with OSA and normal GCA ( P < .001), and they reliably discriminated GCA status (AUC: 0.977; P < .0001). Conclusions Pediatric OSA is associated with overnight increases in urinary concentrations of catecholamines indicative of heightened sympathetic outflow. Increases in GABA levels and decreases in taurine levels could underlie mechanisms of neuronal excitotoxicity and dysfunction. Combinatorial approaches using defined cutoffs in overnight changes in concentrations of selected neurotransmitters in urine may not only predict OSA but also the presence of cognitive deficits. Larger cohort studies appear warranted to confirm these findings.
Hot Jupiters seem to get rarer with decreasing stellar mass. The goal of the Pan-Planets transit survey was the detection of such planets and a statistical characterization of their frequency. Here, ...we announce the discovery and validation of two planets found in that survey, Wendelstein-1b and Wendelstein-2b, which are two short-period hot Jupiters that orbit late K host stars. We validated them both by the traditional method of radial velocity measurements with the HIgh Resolution Echelle Spectrometer and the Habitable-zone Planet Finder instruments and then by their Transit Color Signature (TraCS). We observed the targets in the wavelength range of 4000−24 000 Å and performed a simultaneous multiband transit fit and additionally determined their thermal emission via secondary eclipse observations. Wendelstein-1b is a hot Jupiter with a radius of 1.0314
−0.0061
+0.0061
R
J
and mass of 0.592
−0.129
+0.0165
M
J
, orbiting a K7V dwarf star at a period of 2.66 d, and has an estimated surface temperature of about 1727
−90
+78
K. Wendelstein-2b is a hot Jupiter with a radius of 1.1592
−0.0210
+0.0204
R
J
and a mass of 0.731
−0.311
+0.0541
M
J
, orbiting a K6V dwarf star at a period of 1.75 d, and has an estimated surface temperature of about 1852
−140
+120
K. With this, we demonstrate that multiband photometry is an effective way of validating transiting exoplanets, in particular for fainter targets since radial velocity follow-up becomes more and more costly for those targets.
New insights into Lyme disease Peacock, Brandon N; Gherezghiher, Teshome B; Hilario, Jennifer D ...
Redox biology,
08/2015, Letnik:
5
Journal Article
Recenzirano
Odprti dostop
Lyme borreliosis is transmitted through the bite of a tick that is infected by the bacterial spirochete Borrelia burgdorferi. Clinical manifestation of the disease can lead to heart conditions, ...neurological disorders, and inflammatory disorders. Oxidative stress has been implicated in the pathogenesis of many human diseases. The aim of this study was to investigate the mechanisms of oxidative stress and intracellular communication in Lyme borreliosis patients. Mitochondrial superoxide and cytosolic ionized calcium was measured in peripheral blood mononuclear cells (PBMCs) of Lyme borreliosis patients and healthy controls. Mitochondrial superoxide levels were significantly higher (p<0.0001) in Lyme borreliosis patients (n=32) as compared to healthy controls (n=30). Significantly low (p<0.0001) levels of cytosolic ionized calcium were also observed in Lyme borreliosis patients (n=11) when compared to healthy controls (n=11). These results indicate that there is an imbalance of reactive oxygen species and cytosolic calcium in Lyme borreliosis patients. The results further suggest that oxidative stress and interrupted intracellular communication may ultimately contribute to a condition of mitochondrial dysfunction in the immune cells of Lyme borreliosis patients.
Lyme Borreliosis is an infectious disease caused by the spirochete Borrelia burgdorferi that is transmitted through the bite of infected ticks. Both B cell-mediated humoral immunity and T cell ...immunity develop during natural Borrelia infection. However, compared with humoral immunity, the T cell response to Borrelia infection has not been well elucidated. In this study, a novel T cell-based assay was developed and validated for the sensitive detection of antigen-specific T cell response to B. burgdorferi. Using interferon-g as a biomarker, we developed a new enzyme-linked immunospot method (iSpot Lyme™) to detect Borrelia antigen-specific effector/memory T cells that were activated in vivo by exposing them to recombinant Borrelia antigens ex vivo. To test this new method as a potential laboratory diagnostic tool, we performed a clinical study with a cohort of Borrelia positive patients and healthy controls. We demonstrated that the iSpot Lyme assay has a significantly higher specificity and sensitivity compared with the Western Blot assay that is currently used as a diagnostic measure. A comprehensive evaluation of the T cell response to Borrelia infection should, therefore, provide new insights into the pathogenesis, diagnosis, treatment and monitoring of Lyme disease.
Depression is a common disorder with physical and psychological manifestations often associated with low serotonin. Since noninvasive diagnostic tools for depression are sparse, we evaluated the ...clinical utility of a novel ELISA for the measurement of serotonin in urine from depressed subjects and from subjects under antidepressant therapy. We developed a competitive ELISA for direct measurement of serotonin in derivatized urine samples. Assay performance was evaluated and applied to clinical samples. The analytical range of the assay was from 6.7 to 425 μg serotonin/g creatinine (Cr). The limit of quantification was 4.7 μg/g Cr. The average recovery for spiked urine samples was 104.4%. Average intra-assay variation was 4.4%, and inter-assay variation was <20%. The serotonin analysis was very specific. No significant interferences were observed for 44 structurally and nonstructurally related urinary substances. Very good correlation was observed between urinary serotonin levels measured by ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS; ELISA = 1.16 × LC-MS/MS − 53.8;
r
= 0.965; mean % bias = 11%;
n
= 18). Serotonin was stable in acidified urine for 30 days at room temperature and at −20 °C. The established reference range for serotonin was 54–366 μg/g Cr (
n
= 64). Serotonin levels detected in depressed patients (87.53 ± 4.89 μg/g Cr;
n
= 60) were significantly lower (
p
< 0.001) than in nondepressed subjects (153.38 ± 7.99 μg/g Cr). Urinary excretion of serotonin in depressed individuals significantly increased after antidepressant treatment by 5-hydroxy-tryptophane and/or selective serotonin re-uptake inhibitor (
p
< 0.01). The present ELISA provides a convenient and robust method for monitoring urinary serotonin. It is suitable to monitor serotonin imbalances and may be particularly helpful in evaluating antidepressant therapies.
Figure
Monitoring urinary serotonin by ELISA in depressed patients under antidepressant therapy by 5-HTP, SSRIs and a combination of both
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent a series of upgrades, involving the ...exchange of the MAGIC-I camera and its trigger system, as well as the upgrade of the readout system of both telescopes. We use observations of the Crab Nebula taken at low and medium zenith angles to assess the key performance parameters of the MAGIC stereo system. For low zenith angle observations, the standard trigger threshold of the MAGIC telescopes is ∼ 50GeV. The integral sensitivity for point-like sources with Crab Nebula-like spectrum above 220GeV is (0.66 ± 0.03)% of Crab Nebula flux in 50h of observations. The angular resolution, defined as the σ of a 2-dimensional Gaussian distribution, at those energies is ≲ 0.07°, while the energy resolution is 16%. We also re-evaluate the effect of the systematic uncertainty on the data taken with the MAGIC telescopes after the upgrade. We estimate that the systematic uncertainties can be divided in the following components: < 15% in energy scale, 11%–18% in flux normalization and ± 0.15 for the energy spectrum power-law slope.
The MAGIC telescopes are two Imaging Atmospheric Cherenkov Telescopes (IACTs) located on the Canary island of La Palma. The telescopes are designed to measure Cherenkov light from air showers ...initiated by gamma rays in the energy regime from around 50GeV to more than 50TeV. The two telescopes were built in 2004 and 2009, respectively, with different cameras, triggers and readout systems. In the years 2011–2012 the MAGIC collaboration undertook a major upgrade to make the stereoscopic system uniform, improving its overall performance and easing its maintenance. In particular, the camera, the receivers and the trigger of the first telescope were replaced and the readout of the two telescopes was upgraded. This paper (Part I) describes the details of the upgrade as well as the basic performance parameters of MAGIC such as raw data treatment, linearity in the electronic chain and sources of noise. In Part II, we describe the physics performance of the upgraded system.
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