A screen for peptide agonists of the G-CSF receptor

<p>Abstract</p> <p>Background</p> <p>Granulocyte-colony stimulating factor (G-CSF) is one of the most important pharmacologically used proteins. Potential uses beyond the stimulation of neutrophilic granulocytes are the treatment of CNS disorders. Disadvantages of the G-CSF protein as a drug are its moderate plasma half-life time and considerable production costs. We therefore conducted a screen for peptide agonists derived from the sequence of human G-CSF.</p> <p>Findings</p> <p>Despite of the high sensitivity of our screening system we could not detect any positive hits in a single peptide approach. In a multiplex approach using a permutation of any combination of 10 different peptides we could also not detect a positive block.</p> <p>Conclusions</p> <p>We conclude that larger coherent parts of the protein or dimerising peptides may be needed to achieve activation of the receptor.</p

Satellite-based analysis of clouds and radiation properties of different vegetation types in the Brazilian Amazon region

Land-use changes impact the energy balance of the Earth system, and feedbacks in the Earth system can dampen or amplify this perturbation. We analyze here from satellite data the response of clouds and subsequently radiation to a change of land use for the example of deforestation in the Amazon Basin. In this region, the characteristics of different cloud types over two vegetation types (forest and crop-/grasslands) were calculated for a time period of five years by using satellite data from the instruments MODIS and CERES. The cloud types are defined according to height, optical thickness, and fraction of cloud cover. For calculating the radiative forcing caused by deforestation, the dependency of spatial and temporal averages for the reflected shortwave and outgoing longwave radiation of the top of the atmosphere on vegetation types were determined as well. The results show distinct differences in cloud cover and radiative forcing over crop-/grasslands and forests for the two vegetation regimes, implying a potentially significant positive cloud feedback to deforestation

Formulation of Cannabidiol in Colloidal Lipid Carriers

In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C

Assessing the "Good Life” in a Military Context: How Does Life and Work-Satisfaction Relate to Orientations to Happiness and Career-Success Among Swiss Professional Officers?

The study examines work- and life satisfaction along with orientation to happiness, and their relation to subjective but also objective career success, among Swiss military professional officers. They frequently report worsening of their working conditions due to two reforms that have recently been conducted. A total of N=221 Swiss career officers (mainly Land Forces; from Colonel to First Lieutenant) completed several questionnaires in an online survey. As expected, pleasure, engagement and meaning were positively related to satisfaction with life and the meaningful life also correlated with the (overall) work satisfaction. Higher subjective career success was related to higher satisfaction with life, content-related aspects of work satisfaction, and higher endorsements to the engaged and the meaningful life. Belonging to the general staff was considered as an objective criterion of career success and those who were in the general staff, were higher in their overall work satisfaction, content-related aspects of their work and, again, higher inclination to the life of engagement and the life of meaning. The study suggests that variables of positive psychological functioning are useful additions in the field of military psychology and that they might hold a key for the development of strategies for improving both, work- and life satisfaction among military personne

Nützlichkeit und Zukunft von Distance Education aus Sicht Studierender und Unterrichtender

Um Distance Education auch nach der Pandemie möglichst effektiv gestalten zu können, wurde mit einer Umfrage die Nützlichkeit von Onlineunterrichtsformaten (synchron vs. asynchron) und der gewünschte zukünftige Anteil an Distance Education aus Sicht von Studierenden und Unterrichtenden untersucht. Synchrone Lerneinheiten wurden dabei insgesamt als hilfreicher eingeschätzt. Der gewünschte Anteil an Distance Education (34–50%) fiel bei den Studierenden höher aus als bei den Unterrichtenden. Bestehende Vorerfahrung mit Distance Education führte bei den Studierenden zum Teil zu signifikanten Unterschieden in Bezug darauf, für wie hilfreich sie einzelne Unterrichtsformate beurteilten

Verifying Pragmatic Inferences in Context: An Experimental Comparison of Presuppositions of again and the Definite Determiner with Scalar Implicatures

Contribution to Linguistic Evidence 202

The Effect of Vestibulo-Ocular Reflex Deficits and Covert Saccades on Dynamic Vision in Opioid-Induced Vestibular Dysfunction

Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and experience disturbing oscillopsia. To compensate for the deficient vestibulo-ocular reflex (VOR), they have to rely on refixation saccades. Some can trigger "covert'' saccades while the head still moves; others only initiate saccades afterwards. Due to their shorter latency, it has been hypothesized that covert saccades are particularly beneficial to improve dynamic visual acuity, reducing oscillopsia. Here, we investigate the combined effect of covert saccades and the VOR on clear vision, using the Head Impulse Testing Device - Functional Test (HITD-FT), which quantifies reading ability during passive high-acceleration head movements. To reversibly decrease VOR function, fourteen healthy men (median age 26 years, range 2131) were continuously administrated the opioid remifentanil intravenously (0.15 mu g/kg/min). VOR gain was assessed with the video head-impulse test, functional performance (i.e. reading) with the HITD-FT. Before opioid application, VOR and dynamic reading were intact (head-impulse gain: 0.87 +/- 0.08, mean +/- SD;HITD-FT rate of correct answers: 90 +/- 9%). Remifentanil induced impairment in dynamic reading (HITD-FT 26 +/- 15%) in 12/14 subjects, with transient bilateral vestibular dysfunction (head-impulse gain 0.63 +/- 0.19). HITD-FT score correlated with head-impulse gain (R = 0.63, p = 0.03) and with gain difference (before/with remifentanil, R = -0.64, p = 0.02). One subject had a non-pathological head-impulse gain (0.82 +/- 0.03) and a high HITD-FT score (92%). One subject triggered covert saccades in 60% of the head movements and could read during passive head movements (HITD-FT 93%) despite a pathological head-impulse gain (0.59 +/- 0.03) whereas none of the 12 subjects without covert saccades reached such high performance. In summary, early catch-up saccades may improve dynamic visual function. HITD-FT is an appropriate method to assess the combined gaze stabilization effect of both VOR and covert saccades (overall dynamic vision), e.g., to document performance and progress during vestibular rehabilitation