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The purpose of this study was to investigate whether a six-week, twice weekly resistance training (4 sets at 30% 1-RM until failure) with practical blood flow restriction (BFR) using 7cm wide cuffs with a twist lock placed below the patella is superior to training without BFR (NoBFR) concerning muscle mass and strength gains in calf muscles.
A two-group (BFR n = 12, mean age 27.33 (7.0) years, training experience 7.3 (7.0) years; NoBFR n = 9, mean age 28.9 (7.4) years, training experience 7.1 (6.6) years) randomized matched pair design based on initial 1-RM was used to assess the effects on structural and functional adaptations in healthy males (Perometer calf volume [CV], gastrocnemius muscle thickness using ultrasound [MT], 7-maximal hopping test for leg stiffness [LS], 1-RM smith machine calf raise [1-RM], and visual analogue scale as a measure of pain intensity [VAS]).
The mean number of repetitions completed per training session across the intervention period was higher in the NoBFR group compared to the BFR group (70 (16) vs. 52 (9), p = 0.002). VAS measured during the first session increased similarly in both groups from first to fourth set (p<0.001). No group effects or time×group interactions were found for CV, MT, LS, and 1-RM. However, there were significant time effects for MT (BFR +0.07 cm; NoBFR +0.04; p = 0.008), and 1-RM (BFR +40 kg; NoBFR +34 kg; p<0.001).
LS and CV remained unchanged through training. VAS in both groups were similar, and BFR and NoBFR were equally effective for increasing 1-RM and MT in trained males. However, BFR was more time efficient, due to lesser repetition per training session.
Uni-Highlights Juni/Juli 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
Uni-Highlights Mai/Juni 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
In this work a nonlinear evolution of pure states of a finite dimensional quantum system is introduced, in particular a Riccati evolution equation.
It is shown how this class of dynamics is actually a Hamiltonian dynamics in the complex projective space.
In this projective space it is shown that there is a nonlinear superposition rule, consistent with its linear counterpart in the Hilbert space. As an example, the developed nonlinear formalism is applied to the semiclassical Jaynes–Cummings model.
Later, it is shown that there is an inherent nonlinear evolution in the dynamics of the so-called generalized coherent states.
To show this, the fact that in quantum mechanics it is possible to immerse a ''classical'' manifold into the Hilbert space is employed, such that one may parametrize the time-dependence of the wave function through the variation of parameters in the classical manifold.
The immersion allows to consider the so-called principle of analogy, i.e. using the procedures and structures available from the classical setting to employ them in the quantum setting.
Finally, it is introduced the contact Hamiltonian mechanics, an extension of symplectic Hamiltonian mechanics, and it is showed that it is a natural candidate for a geometric description of non-dissipative and dissipative systems.
Background: Cytokines are mediators of inflammation that contribute to a low-grade inflammation in different disorders like major depression and obesity. It still remains unclear which psychological and medical factors interact with cytokine regulation. In the current investigation, the association between levels of pro-and anti-inflammatory cytokines and anthropometrics, mood state (depressiveness), physical activity and sleep were investigated in a sample of community-dwelled adults.
Methods: Forty-nine subjects met the inclusion criteria for analyses and were assessed at two time-points (baseline (T1) and follow-up (T2), average T1-T2-interval = 215 days). Serum cytokine measures included the pro-inflammatory cytokines interleukin (IL)-2, IL-12, IFN-γ and TNF-α, the anti-inflammatory cytokines IL-4, IL-5, IL-10 and IL-13 and the granulocyte-macrophage colony-stimulating factor (GM-CSF); anthropometrics were assessed via physical examination, depressiveness was assessed via Beck Depression Inventory (BDI)2, parameters of physical activity (steps, METs) and sleep (night/total sleep duration) were measured via a 1-week actigraphy.
Results: Correlation analyses showed low-to moderate significant relationships between the majority of cytokines and the BDI2 at T1, positive correlation with weight and BMI at T1 and T2, and negative correlations with the number of steps and METs at T2 and T2. Regression analyses for T1 revealed that the BDI2 score was the best positive predictor for the concentrations of all nine cytokines, followed by the number of steps and the nightsleep duration as negative predictors. At T2, the amount of steps was found to be negatively associated with IL-4, IL5, IL-10, GM-CSF, IFN-γ, and TNF-α, whereas the BMI could significantly predict IL-12 and IL-13. The BDI2-score was not significantly associated with any of the cytokines. No associations could be found between dynamics in cytokines from T1 and T2 and changes in any of the variables.
Discussion: The present results indicate an influence of physical activity, subjective well-being and body composition on inflammatory mediators. Since there was no standardized intervention targeting the independent variables between T1 and T2, no assumptions on causality can be drawn from the association results.
Here, we describe a new immersion-based clearing method suitable for optical clearing of thick adult human brain samples while preserving its lipids and lipophilic labels such as 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). This clearing procedure is simple, easy to implement, and allowed for clearing of 5 mm thick human brain tissue samples within 12 days. Furthermore, we show for the first time the advantageous effect of the Periodate-Lysine-Paraformaldehyde (PLP) fixation as compared to the more commonly used 4% paraformaldehyde (PFA) on clearing performance.
Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.
Most fungal fatty acid synthases assemble from two multidomain subunits, α and β, into a heterododecameric FAS complex. It has been recently shown that the complex assembly occurs in a cotranslational manner and is initiated by an interaction between the termini of α and β subunits. This initial engagement of subunits may be the rate-limiting phase of the assembly and subject to cellular regulation. Therefore, we hypothesized that bypassing this step by genetically fusing the subunits could be beneficial for biotechnological production of fatty acids. To test the concept, we expressed fused FAS subunits engineered for production of octanoic acid in Saccharomyces cerevisiae. Collectively, our data indicate that FAS activity is a limiting factor of fatty acid production and that FAS fusion proteins show a superior performance compared to their split counterparts. This strategy is likely a generalizable approach to optimize the production of fatty acids and derived compounds in microbial chassis organisms.
Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, is a pleiotropic bioactive lipid mediator capable of evoking complex immune phenomena. Studies have highlighted its importance regarding intracellular signaling cascades as well as membrane-bound S1P receptor (S1PR) engagement in various clinical conditions. In neurological disorders, the S1P–S1PR axis is acknowledged in neurodegenerative, neuroinflammatory, and cerebrovascular disorders. Modulators of S1P signaling have enabled an immense insight into fundamental pathological pathways, which were pivotal in identifying and improving the treatment of human diseases. However, its intricate molecular signaling pathways initiated upon receptor ligation are still poorly elucidated. In this review, the authors highlight the current evidence for S1P signaling in neurodegenerative and neuroinflammatory disorders as well as stroke and present an array of drugs targeting the S1P signaling pathway, which are being tested in clinical trials. Further insights on how the S1P–S1PR axis orchestrates disease initiation, progression, and recovery may hold a remarkable potential regarding therapeutic options in these neurological disorders.
Ziel des Lehr-Lern-Projektes war die Schaffung einer kollegialen Arbeitsgemeinschaft zwischen Lehramtsstudierenden der hochschulischen Ausbildungsphase und bereits im Beruf etablierten Lehrkräften im Fachbereich Geschichte. Traditionell hierarchische Strukturen wurden aufgebrochen, um die jeweiligen Kompetenzen der Teilnehmenden für beide Seiten gewinnbringend zu vereinen. Anders als in den hochschulischen Praktika treten Lehramtsstudierende den Lehrkräften mit Expertise gegenüber: Der Austausch ist daher weniger einseitig als vielmehr von doppelseitigem Nutzen. Dieses Konzept bietet im Sinne einer community of practice nicht nur den Lehramtsstudierenden die Chance, ihr theoretisch erworbenes Wissen praxisorientiert anzuwenden und zu reflektieren, sondern ermöglicht auch den Lehrkräften, an den aktuellen geschichtsdidaktischen Forschungen und Entwicklungen an den Hochschulen teilzuhaben und mithilfe der Studierenden in der eigenen Schulpraxis zu reflektieren und gegebenenfalls anzuwenden. Anliegen des Lehr-Lern-Projektes ist ein Plädoyer, das Potenzial der Hochschulen über die eigenen Studierenden im Fortbildungsbereich der Lehrkräfte gewinnbringend zu nutzen, die schulische Reichweite von fachdidaktischer For-schung auszuschöpfen und den Lehramtsstudierenden zugleich eine weitere Möglichkeit einer schulpraktischen Erfahrung zu bieten. Nicht zuletzt: Die Verzahnung von Ausbildungs- und Weiterbildungsphase ist eine weitere gewinnbringende Möglichkeit, Akteur*innen der Lehrer*innenbildung in einen gewinnbringenden und praxisnahen Dialog zu bringen.
Envy, the inclination to compare rewards, can be expected to unfold when inequalities in terms of pay-off differences are generated in competitive societies. It is shown that increasing levels of envy lead inevitably to a self-induced separation into a lower and an upper class. Class stratification is Nash stable and strict, with members of the same class receiving identical rewards. Upper-class agents play exclusively pure strategies, all lower-class agents the same mixed strategy. The fraction of upper-class agents decreases progressively with larger levels of envy, until a single upper-class agent is left. Numerical simulations and a complete analytic treatment of a basic reference model, the shopping trouble model, are presented. The properties of the class-stratified society are universal and only indirectly controllable through the underlying utility function, which implies that class-stratified societies are intrinsically resistant to political control. Implications for human societies are discussed. It is pointed out that the repercussions of envy are amplified when societies become increasingly competitive.
Tsetse flies are the transmitting vector of trypanosomes causing human sleeping sickness and animal trypanosomiasis in sub-saharan Africa. 3-alkylphenols are used as attractants in tsetse fly traps to reduce the spread of the disease. Here we present an inexpensive production method for 3-ethylphenol (3-EP) and 3-propylphenol (3-PP) by microbial fermentation of sugars. Heterologous expression in the yeast Saccharomyces cerevisiae of phosphopantetheinyltransferase-activated 6-methylsalicylic acid (6-MSA) synthase (MSAS) and 6-MSA decarboxylase converted acetyl-CoA as a priming unit via 6-MSA into 3-methylphenol (3-MP). We exploited the substrate promiscuity of MSAS to utilize propionyl-CoA and butyryl-CoA as alternative priming units and the substrate promiscuity of 6-MSA decarboxylase to produce 3-EP and 3-PP in yeast fermentations. Increasing the formation of propionyl-CoA by expression of a bacterial propionyl-CoA synthetase, feeding of propionate and blocking propionyl-CoA degradation led to the production of up to 12.5 mg/L 3-EP. Introduction of a heterologous ‘reverse ß-oxidation’ pathway provided enough butyryl-CoA for the production of 3-PP, reaching titers of up to 2.6 mg/L. As the concentrations of 3-alkylphenols are close to the range of the concentrations deployed in tsetse fly traps, the yeast broths might become promising and inexpensive sources for attractants, producible on site by rural communities in Africa.
The crystal structure of MgCO3-II has long been discussed in the literature where DFT-based model calculations predict a pressure-induced transition of the carbon atom from the sp2 to the sp3 type of bonding. We have now determined the crystal structure of iron-bearing MgCO3-II based on single-crystal X-ray diffraction measurements using synchrotron radiation. We laser-heated a synthetic (Mg0.85Fe0.15)CO3 single crystal at 2500 K and 98 GPa and observed the formation of a monoclinic phase with composition (Mg2.53Fe0.47)C3O9 in the space group C2/m that contains tetrahedrally coordinated carbon, where CO44− tetrahedra are linked by corner-sharing oxygen atoms to form three-membered C3O96− ring anions. The crystal structure of (Mg0.85Fe0.15)CO3 (magnesium iron carbonate) at 98 GPa and 300 K is reported here as well. In comparison with previous structure-prediction calculations and powder X-ray diffraction data, our structural data provide reliable information from experiments regarding atomic positions, bond lengths, and bond angles.
A new pseudopolymorph of perchlorinated neopentasilane: the benzene monosolvate Si(SiCl3)4·C6H6
(2020)
A new pseudopolymorph of dodecachloropentasilane, namely a benzene monosolvate, Si5Cl12·C6H6, is described. There are two half molecules of each kind in the asymmetric unit. Both Si5Cl12 molecules are completed by crystallographic twofold symmetry. One of the benzene molecules is located on a twofold rotation axis with two C—H groups located on this rotation axis. The second benzene molecule has all atoms on a general position: it is disordered over two equally occupied orientations. No directional interactions beyond normal van der Waals contacts occur in the crystal.
In this report, we present the contributions, outcomes, ideas, discussions and conclusions obtained at the PaleoMaps Workshop 2019, that took place at the Institute of Geography of the University of Cologne on 23 and 24 September 2019. The twofold aim of the workshop was: (1) to provide an overview of approaches and methods that are presently used to incorporate paleoenvironmental information in human–environment interaction modeling applications, and building thereon; (2) to devise new approaches and solutions that might be used to enhance the reconstruction of past human–environmental interconnections. This report first outlines the presented papers, and then provides a joint protocol of the often extensive discussions that came up following the presentations or else during the refreshment intervals. It concludes by adressing the open points to be resolved in future research avenues, e.g., implementation of open science practices, new procedures for reviewing of publications, and future concepts for quality assurance of the often complex paleoenvironmental data. This report may serve as an overview of the state of the art in paleoenvironment mapping and modeling. It includes an extensive compilation of the basic literature, as provided by the workshop attendants, which will itself facilitate the necessary future research.
Joschua Yesni Arnaut verwebt sein künstlerisches Schaffen eng mit seinen persönlichen Erfahrungen: In "Didn’t We Deserve A Look At You The Way You Really Are?" in der Schleuse der Rüsselheimer Opelvillen stellt er das Thema Gewalt in den Mittelpunkt. Ein Gespräch über Neurosen, Privilegien und den Charme des Zufalls.
This article provides a proposal to use IMF Article VIII, Section 2 (b) to establish a binding mechanism on private creditors for a sovereign debt standstill. The proposal builds on the original idea by Whitney Deveboise (1984). Using arguments brought forward by confidential IMF staff papers (1988, 1996) and the IMF General Counsel (1988), this paper shows how an authoritative interpretation of Article VIII, Section 2 (b) can provide protection from litigation to countries at risk of debt distress.
The envisaged mechanism presents several advantages over recent proposals for a binding standstill mechanism, such as the International Developing Country Debt Authority (IDCDA) by UNCTAD and a Central Credit Facility (CFF) by the Bolton Committee. First, this approach would not require the creation of new intergovernmental mechanisms or facilities. Second, the activation of the standstill mechanism can be set in motion by any IMF member country and does not require a modification of its Articles of Agreement. Third, debtor countries acting in good faith under an IMF program would be protected from aggressive litigation strategies from holdout creditors in numerous jurisdictions, including the US and the UK. Fourth, courts in key jurisdictions would avoid becoming overburdened by a cascade of sovereign debt litigation covering creditors and debtors across the globe. Fifth, private creditors would receive uniform treatment and ensure intercreditor equality. Sixth and last, the mechanism would provide additional safeguards to protect emergency multilateral financing provided to tackle Covid-19.
Using a novel experimental design, I test how the exposure to information about a group’s relative performance causally affects the members’ level of identification and thereby their propensity to harm affiliates of comparison groups. I find that both, being informed about a high and poor relative performance of the ingroup similarly fosters identification. Stronger ingroup identification creates increased hostility against the group of comparison. In cases where participants learn about poor relative performance, there appears to be a direct level effect additionally elevating hostile discrimination. My findings shed light on a specific channel through which social media may contribute to intergroup fragmentation and polarization.
Measurements of halogenated trace gases in ambient air frequently rely on canister sampling followed by offline laboratory analysis. This allows for a large number of compounds to be analysed under stable conditions, maximizing measurement precision. However, individual compounds might be affected during the sampling and storage of canister samples. In order to assess halocarbon stability in whole-air samples from the upper troposphere and lowermost stratosphere, we performed stability tests using the high-resolution sampler (HIRES) air sampling unit, which is part of the Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container (CARIBIC) instrument package. The HIRES unit holds 88 lightweight stainless-steel cylinders that are pressurized in flight to 4.5 bar using metal bellows pumps. The HIRES unit was first deployed in 2010 but has up to now not been used for regular halocarbon analysis with the exception of chloromethane analysis. The sample collection unit was tested for the sampling and storage effects of 28 halogenated compounds. The focus was on compound stability in the stainless-steel canisters during storage of up to 5 weeks and on the influence of ozone, since flights take place in the upper troposphere and lowermost stratosphere with ozone mixing ratios of up to several hundred parts per billion by volume (ppbv). Most of the investigated (hydro)chlorofluorocarbons and long-lived hydrofluorocarbons were found to be stable over a storage time of up to 5 weeks and were unaltered by ozone being present during pressurization. Some compounds such as dichloromethane, trichloromethane, and tetrachloroethene started to decrease in the canisters after a storage time of more than 2 weeks or exhibited lowered mixing ratios in samples pressurized with ozone present. A few compounds such as tetrachloromethane and tribromomethane were found to be unstable in the HIRES stainless-steel canisters independent of ozone levels. Furthermore, growth was observed during storage for some species, namely for HFC-152a, HFC-23, and Halon 1301.
Background: Myocardial perfusion with cardiovascular magnetic resonance (CMR) imaging is an established diagnostic test for evaluation of myocardial ischaemia. For quantification purposes, the 16 segment American Heart Association (AHA) model poses limitations in terms of extracting relevant information on the extent/severity of ischaemia as perfusion deficits will not always fall within an individual segment, which reduces its diagnostic value, and makes an accurate assessment of outcome data or a result comparison across various studies difficult. We hypothesised that division of the myocardial segments into epi- and endocardial layers and a further circumferential subdivision, resulting in a total of 96 segments, would improve the accuracy of detecting myocardial hypoperfusion. Higher (sub-)subsegmental recording of perfusion abnormalities, which are defined relatively to the normal reference using the subsegment with the highest value, may improve the spatial encoding of myocardial blood flow, based on a single stress perfusion acquisition. Objective: A proof of concept comparison study of subsegmentation approaches based on transmural segments (16 AHA and 48 segments) vs. subdivision into epi- and endocardial (32) subsegments vs. further circumferential subdivision into 96 (sub-)subsegments for diagnostic accuracy against invasively defined obstructive coronary artery disease (CAD). Methods: Thirty patients with obstructive CAD and 20 healthy controls underwent perfusion stress CMR imaging at 3 T during maximal adenosine vasodilation and a dual bolus injection of 0.1mmol/kg gadobutrol. Using Fermi deconvolution for blood flow estimation, (sub-)subsegmental values were expressed relative to the (sub)subsegment with the highest flow. In addition, endo−/epicardial flow ratios were calculated based on 32 and 96 (sub-)subsegments. A receiver operating characteristics (ROC) curve analysis was performed to compare the diagnostic performance of discrimination between patients with CAD and healthy controls. Observer reproducibility was assessed using Bland-Altman approaches. Results: Subdivision into more and smaller segments revealed greater accuracy for #32, #48 and # 96 compared to the standard #16 approach (area under the curve (AUC): 0.937, 0.973 and 0.993 vs 0.820, p<0.05). The #96-based endo−/epicardial ratio was superior to the #32 endo−/epicardial ratio (AUC 0.979, vs. 0.932, p<0.05). Measurements for the #16 model showed marginally better reproducibility compared to #32, #48 and #96 (mean difference± standard deviation: 2.0±3.6 vs. 2.3±4.0 vs 2.5±4.4 vs. 4.1±5.6). Conclusions: Subsegmentation of the myocardium improves diagnostic accuracy and facilitates an objective cutoff-based description of hypoperfusion, and facilitates an objective description of hypoperfusion, including the extent and severity of myocardial ischaemia. Quantification based on a single (stress-only) pass reduces the overall amount of gadolinium contrast agent required and the length of the overall diagnostic study.
Körpersymmetrie gilt unter Evolutionswissenschaftlern als Hinweis auf eine stabile Entwicklungsgeschichte von der Eizelle bis hin zum erwachsenen Lebewesen mit daraus resultierender Gesundheit. Symmetrie steht für gute Abwehrmechanismen trotz einflussnehmender Störfaktoren, die allgegenwärtig sind. Symmetrische Körper und Gesichter werden vom anderen Geschlecht bevorzugt und als attraktiver bewertet. Das Gegenstück der Symmetrie bildet die fluktuierende Asymmetrie als Abweichung von perfekter, bilateraler Symmetrie an verschiedenen Stellen des Körpers. Symmetrie kann somit als Fitnessindikator angesehen werden, also als ein Merkmal des erfolgreichen Umwerbens in der Partnerwahl. Dies geschieht typischerweise durch die Entwicklung eines Merkmals oder durch aufwändigeres Verhalten, dessen Ausbildung für ein weniger „fittes“ Individuum zu kostspielig wäre. Die Kernfragen der vorliegenden Studie waren, ob sich diese Anforderung des Fitnessindikators Symmetrie auf die verborgene Struktur des Kehlkopfes übertragen lässt und ob die Asymmetrie des Kehlkopfes mit der Attraktivität der Stimme assoziiert ist. Die fluktuierende Asymmetrie des Larynx wurde bisher noch nicht untersucht. An der Untersuchung nahmen 80 Versuchspersonen im Alter von 20 bis 70 Jahren teil. Hauptzielgrößen waren Larynxasymmetrie und Stimmattraktivität. Die Larynxasymmetrie wurde mittels Videolaryngostroboskopie und anschließender Asymmetriebewertung auf einer 7-stufigen Skala durch Experten erfasst. Die Attraktivität der Stimme wurde auf Basis eines vorgelesenen phonetischen Standardtexts durch Dritte bewertetet. Weitere Variablen waren die Gesichtsasymmetrie, die durch Vermessung von Fotografien bestimmt wurde, und die durch Dritte bewertete Gesichtsattraktivität. Mit Hilfe eines Fragebogens, der abgesehen von Alter, Geschlecht, Anzahl bisheriger Sexualpartner, Erkältungskrankheiten im vorherigen Jahr sowie eingenommener Medikamente und das Rauchverhalten die Beschwerdenliste nach Zerssen (1976) und die Kurzfassung des Voice Handicap Index (VHI-12) enthielt, wurde versucht, die Gesundheit zu registrieren. Darüber hinaus erbat der Fragebogen bei weiblichen Probanden Angaben zum Menstruationszyklus, um die Fertilität zum Messzeitpunkt zu erfassen. Der Erfassung der Körperkonstitution dienten die Messungen von Größe und Gewicht, des Körperfettanteils und der Muskelmasse sowie die Umfangsbestimmung von Hals, Schulter, Brust, Taille, Hüfte und Bizeps. Das 2D:4D-Längenverhältnis wurde mit Hilfe einer Fotokopie der palmaren Handseite als Indikator für pränatales Testosteron ermittelt. Der zentrale Zusammenhang zwischen Stimmattraktivität und Larynxasymmetrie bestätigte sich nur für Männer. Für diese bestand außerdem eine positive Relation der Stimmattraktivität mit dem Schulter-Hüft-Verhältnis und dem Verhältnis von Brust zu Taille, d. h. Stimmen von Männern mit verhältnismäßig breiter Schulter und breiter Brust wurden attraktiver bewertet. Umgekehrt galt: Je niedriger der BMI, Körperfettanteil, Halsumfang, das Alter und die Anzahl eingenommener rezeptpflichtiger Medikamente, umso höher war die Attraktivitätsbewertung ihrer Stimme. Weibliche Stimmen wurden umso attraktiver bewertet, je jünger die Frauen waren, je größer das Brust-Taille- Verhältnis, je niedriger das Taille Hüft-Verhältnis, je geringen der Halsumfang, je niedriger der Stimmstörungsindex (VHI-12) und je weniger Zigaretten sie geraucht haben. Erwartungsgemäß korrelierte die Larynxasymmetrie bei Männern signifikant negativ mit der Gesichtsattraktivität sowie beinahe signifikant mit dem Schulter-Hüft-Verhältnis. Männliche Larynges wurden außerdem asymmetrischer bewertet, je älter die Person, je höher der BMI, der Körperfettanteil, der Halsumfang und die Anzahl eingenommener Medikamente war. Für Frauen einzig (positiv) signifikant wurde der Zusammenhang zwischen Larynxasymmetrie und Nikotinabusus. Die zusätzlich erfolgten Regressionsanalysen erzielten ein signifikantes Ergebnis für den Zusammenhang zwischen der Stimmattraktivität mit der Muskelmasse für beide Geschlechter, außerdem gelang es, einen signifikanten Zusammenhang zwischen der Larynxasymmetrie und der SHR bei Männern darzustellen. Die (negativen) Korrelationen zwischen der Larynxasymmetrie für Männer mit Stimm- und Gesichtsattraktivität deuten darauf hin, dass Larynxasymmetrie als Fitnessindikator dienen kann. Darüber hinaus lieferte die vorliegende Studie keine einfach interpretierbaren Ergebisse; häufig waren sie geschlechtsspezifisch. Die Dissertation unterstrich damit die Komplexität der Zusammenhänge und wies auf den Stellenwert von Geschlechterunterschieden hin. Weiterführende Untersuchungen sind nötig, um die Ergebnisse zu bestätigen und um den Stellenwert der Larynxasymmetrie für Frauen zu klären.
Direct nanoscopic observation of plasma waves in the channel of a graphene field-effect transistor
(2020)
Plasma waves play an important role in many solid-state phenomena and devices. They also become significant in electronic device structures as the operation frequencies of these devices increase. A prominent example is field-effect transistors (FETs), that witness increased attention for application as rectifying detectors and mixers of electromagnetic waves at gigahertz and terahertz frequencies, where they exhibit very good sensitivity even high above the cut-off frequency defined by the carrier transit time. Transport theory predicts that the coupling of radiation at THz frequencies into the channel of an antenna-coupled FET leads to the development of a gated plasma wave, collectively involving the charge carriers of both the two-dimensional electron gas and the gate electrode. In this paper, we present the first direct visualization of these waves. Employing graphene FETs containing a buried gate electrode, we utilize near-field THz nanoscopy at room temperature to directly probe the envelope function of the electric field amplitude on the exposed graphene sheet and the neighboring antenna regions. Mapping of the field distribution documents that wave injection is unidirectional from the source side since the oscillating electrical potentials on the gate and drain are equalized by capacitive shunting. The plasma waves, excited at 2 THz, are overdamped, and their decay time lies in the range of 25-70 fs. Despite this short decay time, the decay length is rather long, i.e., 0.3-0.5 μm, because of the rather large propagation speed of the plasma waves, which is found to lie in the range of 3.5-7 × 106 m/s, in good agreement with theory. The propagation speed depends only weakly on the gate voltage swing and is consistent with the theoretically predicted 1/4 power law.
A strong decline and thinning of the Arctic sea-ice cover over the past five decades has been documented. The former multiyear sea-ice system has largely changed to an annual system and with it the dynamics of sea-ice transport across the Arctic Ocean. Less sea ice is reaching the Fram Strait and more ice and ice-transported material is released in the northern Laptev Sea and the central Arctic Ocean. This trend is expected to have a decisive impact on ice associated (“sympagic”) communities. As sympagic fauna plays an important role in transmitting carbon from the ice-water interface to the pelagic and benthic food webs, it is important to monitor its community composition under the changing environmental conditions. We investigated the taxonomic composition, abundance and distribution of sea-ice meiofauna (here heterotrophs >10 μm; eight stations) and under-ice fauna (here metazoans >300 μm; fourteen stations) in Arctic 1.5 year-old pack ice north of Svalbard. Sampling was conducted during spring 2015 by sea-ice coring and trawling with a Surface and Under-Ice Trawl. We identified 42 taxa associated with the sea ice. The total abundance of sea-ice meiofauna ranged between 580 and 17,156 ind.m–2 and was dominated by Ciliophora (46%), Copepoda nauplii (29%), and Harpacticoida (20%). In contrast to earlier studies in this region, we found no Nematoda and few flatworms in our sea-ice samples. Under-ice fauna abundance ranged between 15 and 6,785 ind.m–2 and was dominated by Appendicularia (58%), caused by exceptionally high abundance at one station. Copepoda nauplii (23%), Calanus finmarchicus (9%), and Calanus glacialis (6%) were also very abundant while sympagic Amphipoda were comparatively rare (0.35%). Both sympagic communities showed regional differences in community composition and abundance between shelf and offshore stations, but only for the under-ice fauna those differences were statistically significant. Selected environmental variables moderately explained variations in abundances of both faunas. The results of this study are consistent with predictions of diversity shifts in the new Arctic.
Limb stump pain after amputation, due to sensitized neuromas, is a common condition that can cause a great deal of suffering in affected patients. Treatment is difficult, requiring a multidisciplinary approach that is often unsatisfactory. One treatment used to mitigate pain is electrical stimulation (EStim), administered using several different therapeutic approaches. The research described in this dissertation sought to characterize changes in peripheral nerve morphology, and neuroma formation, following limb amputation, with an eye toward developing better treatment strategies, that intervene before neuromas are fully formed. Another focus of this study was to evaluate the effect EStim has on changes in peripheral nerve morphology, and neuroma formation, following limb amputation.
Right forelimbs of 42 male Sprague Dawley rats were amputated. At 3, 7, 28, 60 and 90 days post amputation (DPA) 6 limb stumps, in each group, were harvested and changes in peripheral nerve morphology, and neuroma formation were measured. In addition, limb stumps of 6 EStim treated, 6 sham-treated (deactivated EStim devices), and 6 non-treated rats were harvested at 28 DPA.
Analysis revealed six distinct morphological characteristics of peripheral nerves during nerve regrowth and neuroma development; 1) normal nerve, 2) degenerating axons, 3) axonal sprouts, 4) unorganized bundles of axons in connective tissue, 5) unorganized axon growth into muscles, and 6) unorganized axon growth into fibrotic tissue (neuroma). At the early stages (3 & 7 DPA), normal nerves could be identified throughout the limb stump tissues and small areas of axonal sprouts were present near the distal tip of the stumps. Signs of degenerating axons were evident from 7 to 90 DPA. From day 28 on, variability of nerve characteristics, with signs of unorganized axon growth into muscle and fibrotic tissue, and neuroma formation, became visible in multiple areas of stump tissue. These pathological features became more evident at 60 and 90 DPA. EStim treated stumps revealed neuroma formation in 1 out of 6 animals, whereas in sham and controls, neuroma formation was seen in 4 out of 6 stumps respectively.
We were able to identify 6 separate histological stages of peripheral nerve regrowth and neuroma formation over 90 days following amputation. Axonal regrowth was observed as early as 3 DPA, and signs of unorganized axonal growth and neuroma formation were evident by 28 DPA. Our observations suggest that EStim-based treatment and/or other prevention strategies might be more effective if administered in the initial dynamic stages of neuroma development.
Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our “hub-spoke” model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.
The permeability and inflammatory tissue reaction to Mucomaix® matrix (MM), a non- cross-linked collagen-based matrix was evaluated in both ex vivo and in vivo settings. Liquid platelet rich fibrin (PRF), a blood concentrate system, was used to assess its capacity to absorb human proteins and interact with blood cells ex vivo. In the in vivo aspect, 12 Wister rats had MM implanted subcutaneously, whereas another 12 rats (control) were sham-operated without biomaterial implantation. On days 3, 15 and 30, explantation was completed (four rats per time-point) to evaluate the tissue reactions to the matrix. Data collected were statistically analyzed using analysis of variance (ANOVA) and Tukey multiple comparisons tests (GraphPad Prism 8). The matrix absorbed the liquid PRF in the ex vivo study. Day 3 post-implantation revealed mild tissue inflammatory reaction with presence of mononuclear cells in the implantation site and on the biomaterial surface (mostly CD68-positive macrophages). The control group at this stage had more mononuclear cells than the test group. From day 15, multinucleated giant cells (MNGCs) were seen in the implantation site and the outer third of the matrix with marked increase on day 30 and spread to the matrix core. The presence of these CD68-positive MNGCs was associated with significant matrix vascularization. The matrix degraded significantly over the study period, but its core was still visible as of day 30 post-implantation. The high permeability and fast degradation properties of MM were highlighted.
Background: Culture-derived mesenchymal stromal cells (MSCs) exhibit variable characteristics when manufactured using different methods and different source materials. The purpose of this study was to assess the impact on MSC characteristics when different laboratories propagated MSCs from cultures initiated with BM aliquots derived from the same donor source material.
Methods and Methods: Five aliquots from each of three different BM donors were distributed to five independent laboratories. Three laboratories plated whole BM and two laboratories a mononuclear BM cell fraction. Four laboratories cultured in media supplemented with fetal bovine serum (FBS) and one laboratory used human platelet lysate (hPL). Initial cell seeding densities (i.e., P0) ranged from 19.7 × 103/cm2–282 × 103/cm2 and for second seeding (i.e., P1) 0.05 × 103–5.1 × 103 cells/cm2. Post-thawed MSCs from each laboratory were analyzed for cell viability, immunophenotype, tri-lineage differentiation, fibroblast colony-forming units (CFU-F), gene expression, and immunosuppressive activity.
Results: Transit times from BM collection to receipt by laboratories located in the United States ranged from 16.0–30.0 h and from 41.5–71.5 h for a laboratory in Asia. Post-thaw culture derived MSCs rom BM #1, #2, and #3 exhibited viabilities that ranged from 74–92%, 61–96%, and 23–90%, respectively. CFU activity from BM #1, #2, and #3 per 200 MSCs plated averaged 45.1 ± 21.4, 49.3 ± 26.8 and 14.9 ± 13.3, respectively. No substantial differences were observed in immunophenotype, and immunosuppressive activities. Global gene expression profiles of MSCs revealed transcriptome differences due to different inter-laboratory methods and to donor source material with the center effects showing greater molecular differences than source material.
Conclusion: Functional and molecular differences exist among MSCs produced by different centers even when the same BM starting material is used to initiate cultures. These results indicated that manufacturing of MSCs by five independent centers contributed more to MSC variability than did the source material of the BM used in this study. Thus, emphasizing the importance of establishing worldwide standards to propagate MSCs for clinical use.
Purpose: In the clinical routine, detection of focal cortical dysplasia (FCD) by visual inspection is challenging. Still, information about the presence and location of FCD is highly relevant for prognostication and treatment decisions. Therefore, this study aimed to develop, describe and test a method for the calculation of synthetic anatomies using multiparametric quantitative MRI (qMRI) data and surface-based analysis, which allows for an improved visualization of FCD.
Materials and Methods: Quantitative T1-, T2- and PD-maps and conventional clinical datasets of patients with FCD and epilepsy were acquired. Tissue segmentation and delineation of the border between white matter and cortex was performed. In order to detect blurring at this border, a surface-based calculation of the standard deviation of each quantitative parameter (T1, T2, and PD) was performed across the cortex and the neighboring white matter for each cortical vertex. The resulting standard deviations combined with measures of the cortical thickness were used to enhance the signal of conventional FLAIR-datasets. The resulting synthetically enhanced FLAIR-anatomies were compared with conventional MRI-data utilizing regions of interest based analysis techniques.
Results: The synthetically enhanced FLAIR-anatomies showed higher signal levels than conventional FLAIR-data at the FCD sites (p = 0.005). In addition, the enhanced FLAIR-anatomies exhibited higher signal levels at the FCD sites than in the corresponding contralateral regions (p = 0.005). However, false positive findings occurred, so careful comparison with conventional datasets is mandatory.
Conclusion: Synthetically enhanced FLAIR-anatomies resulting from surface-based multiparametric qMRI-analyses have the potential to improve the visualization of FCD and, accordingly, the treatment of the respective patients.
Temperature elevations constitute a major threat to plant performance. In recent years, much was learned about the general molecular mode of heat stress reaction of plants. The current research focuses on the integration of the knowledge into more global networks, including the reactions of cellular compartments. For instance, chloroplast function is central for plant growth and survival, and the performance of chloroplasts is tightly linked to the general status of the cell and vice versa. We examined the changes in photosynthesis, chloroplast morphology and proteomic composition posed in Arabidopsis thaliana chloroplasts after a single or repetitive heat stress treatment over a period of two weeks. We observed that the acclimation is potent in the case of repetitive application of heat stress, while a single stress results in lasting alterations. Moreover, the physiological capacity and its adjustment are dependent on the efficiency of the protein translocation process as judged from the analysis of mutants of the two receptor units of the chloroplast translocon, TOC64, and TOC33. In response to repetitive heat stress, plants without TOC33 accumulate Hsp70 proteins and plants without TOC64 have a higher content of proteins involved in thylakoid structure determination when compared to wild-type plants.
A new virus, SARS-CoV-2, emerged in the Chinese city of Wuhan at the end of 2019. Infected persons developed an atypical form of pneumonia, later known as COVID-19. The pathogen created a pandemic, with fatalities throughout the world, and also led to the adoption of restrictive measures which were, until recently, unthinkable, as well as fostering new political conflicts. Even the path of the multilateral order in its current form is at stake. For a take on these issues under international law, the legal regime of the World Health Organization (WHO) and its response to the pandemic provides an insightful access. ...
Since the introduction of rental E-scooters in Germany in mid-June 2019, the safety of this new means of transport has been the subject of extensive public debate. However, valid data on injuries and usage habits are not yet available. This retrospective two-center study included a total of 76 patients who presented to the emergency department following E-scooter-related accidents. The mean age was 34.3 ± 12.4 years and 69.7% of the patients were male. About half of the patients were admitted by ambulance (42.1%). Fractures were found in 48.6% of patients, and 27.6% required surgical treatment due to a fracture. The upper extremities were the most commonly affected body region, followed by injuries to the lower extremity and to the head and face. Only one patient had worn a helmet. In-hospital treatment was necessary for 26.3% of the cases. Patients presented to the emergency department mainly during the weekend and on-call times. This is the first report on E-scooter-related injuries in Germany. Accidents with E-scooters can cause serious injuries and, therefore, represent a further burden to emergency departments. The use of E-scooters appears to be mostly recreational, and the rate of use of protective gear is low.
Transcriptional basis for differential thermosensitivity of seedlings of various tomato genotypes
(2020)
Transcriptional reprograming after the exposure of plants to elevated temperatures is a hallmark of stress response which is required for the manifestation of thermotolerance. Central transcription factors regulate the stress survival and recovery mechanisms and many of the core responses controlled by these factors are well described. In turn, pathways and specific genes contributing to variations in the thermotolerance capacity even among closely related plant genotypes are not well defined. A seedling-based assay was developed to directly compare the growth and transcriptome response to heat stress in four tomato genotypes with contrasting thermotolerance. The conserved and the genotype-specific alterations of mRNA abundance in response to heat stress were monitored after exposure to three different temperatures. The transcripts of the majority of genes behave similarly in all genotypes, including the majority of heat stress transcription factors and heat shock proteins, but also genes involved in photosynthesis and mitochondrial ATP production. In turn, genes involved in hormone and RNA-based regulation, such as auxin- and ethylene-related genes, or transcription factors like HsfA6b, show a differential regulation that associates with the thermotolerance pattern. Our results provide an inventory of genes likely involved in core and genotype-dependent heat stress response mechanisms with putative role in thermotolerance in tomato seedlings.
Did the Federal Reserves’ Quantitative Easing (QE) in the aftermath of the financial crisis have macroeconomic effects? To answer this question, the authors estimate a large-scale DSGE model over the sample from 1998 to 2020, including data of the Fed’s balance sheet. The authors allow for QE to affect the economy via multiple channels that arise from several financial frictions. Their nonlinear Bayesian likelihood approach fully accounts for the zero lower bound on nominal interest rates. They find that between 2009 to 2015, QE increased output by about 1.2 percent. This reflects a net increase in investment of nearly 9 percent, that was accompanied by a 0.7 percent drop in aggregate consumption. Both, government bond and capital asset purchases were effective in improving financing conditions. Especially capital asset purchases significantly facilitated new investment and increased the production capacity. Against the backdrop of a fall in consumption, supply side effects dominated which led to a mild disinflationary effect of about 0.25 percent annually.
Neuronal nitric oxide synthase (NOS-I) impacts on fear/anxiety-like behavior in animals. In humans, the short (S) allele of a functional promotor polymorphism of NOS1 (NOS1 ex1f-VNTR) has been shown to be associated with higher anxiety and altered fear conditioning in healthy subjects in the amygdala and hippocampus (AMY/HIPP). Here, we explore the role of NOS1 ex1f-VNTR as a pathophysiological correlate of panic disorder and agoraphobia (PD/AG). In a sub-sample of a multicenter cognitive behavioral therapy (CBT) randomized controlled trial in patients with PD/AG (n = 48: S/S-genotype n=15, S/L-genotype n=21, L/L-genotype n=12) and healthy control subjects, HS (n = 34: S/S-genotype n=7, S/L-genotype n=17, L/L-genotype=10), a differential fear conditioning and extinction fMRI-paradigm was used to investigate how NOS1 ex1f-VNTR genotypes are associated with differential neural activation in AMY/HIPP. Prior to CBT, L/L-allele carriers showed higher activation than S/S-allele carriers in AMY/HIPP. A genotype × diagnosis interaction revealed that the S-allele in HS was associated with a pronounced deactivation in AMY/HIPP, while patients showed contrary effects. The interaction of genotype × stimulus type (CS+, conditioned stimulus associated with an aversive stimulus vs. CS-, unassociated) showed effects on differential learning in AMY/HIPP. All effects were predominately found during extinction. Genotype associated effects in patients were not altered after CBT. Low statistical power due to small sample size in each subgroup is a major limitation. However, our findings provide first preliminary evidence for dysfunctional neural fear conditioning/extinction associated with NOS1 ex1f-VNTR genotype in the context of PD/AG, shedding new light on the complex interaction between genetic risk, current psychopathology and treatment-related effects.
Introduction: The worldwide spread of the novel coronavirus (SARS-CoV2) has prompted numerous countries to restrict public life. Related measures, such as limits on social gatherings, business closures, or lockdowns, are expected to considerably reduce the individual opportunities to move outside the home. As physical activity (PA) and sport participation significantly contribute to health, this study has two objectives. The objectives of this study are to assess changes in PA and well-being since the coronavirus outbreak in affected countries. Additionally, we will evaluate the impact of digital home-based exercise programs on PA as well as physical and mental health outcomes.
Method: A multinational network trial will be conducted with three planned phases (A, B, and C). Part A consists of administering a structured survey. It investigates changes in PA levels and health during the coronavirus outbreak and measures the preferences of the participants regarding online training programs. Part B is a two-armed randomized-controlled trial. Participants assigned to the intervention group (IG) will complete a digital 4-week home exercise training (live streaming via internet) guided by the survey results on content and time of program. The control group (CG) will not receive the program. Part C is 4-week access of both CG and IG to a digital archive of pre-recorded workouts from Part B. Similar to Part A, questionnaires will be used in both Part B and C to estimate the effects of exercise on measures of mental and physical health.
Results and Discussion: The ASAP project will provide valuable insights into the importance of PA during a global pandemic. Our initial survey is the first to determine how governmental confinement measures impact bodily and mental well-being. Based on the results, the intervention studies will be unique to address health problems potentially arising from losses in PA. If proven effective, the newly developed telehealth programs could become a significant and easy-to-distribute factor in combating PA decreases. Results of the study may hence guide policy makers on methods to maintain PA and health when being forced to restrict public life.
Study Register: DRKS00021273.
Dental clinics were suspected to be a hotspot for nosocomial transmission of coronavirus disease 19 (COVID-19), yet there has been no clear recommendation about emergency dental care and appropriate personal protective equipment during pandemics. In this paper, we aim to summarize recommendations for (i) patient risk assessment, (ii) patient triage, and (iii) measures to prevent infection of health professionals and nosocomial transmission in dental clinics. The available evidence was collected by performing searches on PubMed, Embase, and Cochrane databases. We reviewed papers on COVID-19, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and related respiratory viral diseases. Legal and ethical frameworks, as well as international (e.g., World Health Organization (WHO)) and national (e.g., public health institutes, dental associations) guidelines were screened to summarize recommendations related to dental emergency care. To assess the patient risk, a questionnaire was developed to classify patients at unknown, high, and very high risk. Patient triage recommendations were summarized in a flow chart that graded the emergency level of treatments (i.e., urgent, as soon as possible, and postpone). Measures to prevent disease transmission based on current evidence were grouped for dental health professionals, dental clinics, and patients. The present recommendations may support health professionals implement preventative measures during the pandemic.
Children are commonly exposed to second-hand smoke (SHS) in the domestic environment or inside vehicles of smokers. Unfortunately, prenatal tobacco smoke (PTS) exposure is still common, too. SHS is hazardous to the health of smokers and non-smokers, but especially to that of children. SHS and PTS increase the risk for children to develop cancers and can trigger or worsen asthma and allergies, modulate the immune status, and is harmful to lung, heart and blood vessels. Smoking during pregnancy can cause pregnancy complications and poor birth outcomes as well as changes in the development of the foetus. Lately, some of the molecular and genetic mechanisms that cause adverse health effects in children have been identified. In this review, some of the current insights are discussed. In this regard, it has been found in children that SHS and PTS exposure is associated with changes in levels of enzymes, hormones, and expression of genes, micro RNAs, and proteins. PTS and SHS exposure are major elicitors of mechanisms of oxidative stress. Genetic predisposition can compound the health effects of PTS and SHS exposure. Epigenetic effects might influence in utero gene expression and disease susceptibility. Hence, the limitation of domestic and public exposure to SHS as well as PTS exposure has to be in the focus of policymakers and the public in order to save the health of children at an early age. Global substantial smoke-free policies, health communication campaigns, and behavioural interventions are useful and should be mandatory.
This article investigates the L1 acquisition of different types of direct objects in European Portuguese (EP). Previous research has revealed that although children have early syntactic and pragmatic knowledge of objects across languages, the adequate use of pronouns and null objects is protracted in the acquisition of EP (Costa et al. 2012). The present study shows that children acquiring the distribution of direct objects are aware of universal pragmatic hierarchies but struggle with the interpretation and feature bundles of null objects. Assuming that arguments are linked to left-peripheral C/edge linkers (Sigurðsson 2011), we argue that children need more time to discover the adult-like feature composition of null objects in EP because they involve phi-silent features. Relative accessibility (Ariel 1991) is universal and available early, whereas the absolute accessibility of null objects, i.e. their feature content, is acquired relatively late.
Objectives: Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Methods: Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for the treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. Results: DRV showed no antiviral activity against SARS-CoV-2 at clinically relevant concentrations (EC50 > 100 μM). Remdesivir, used as a positive control, demonstrated potent antiviral activity (EC50 = 0.38 μM). Conclusions: Overall, the data do not support the use of DRV for the treatment of COVID-19.
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential K-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.
Formation of pathological anti-FVIII antibodies, or “inhibitors,” is the most serious complication of therapeutic FVIII infusions, affecting up to 1/3 of severe Hemophilia A (HA) patients. Inhibitor formation is a classical T-cell dependent adaptive immune response. As such, it requires help from the innate immune system. However, the roles of innate immune cells and mechanisms of inhibitor development vs. immune tolerance, achieved with or without Immune Tolerance Induction (ITI) therapy, are not well-understood. To address these questions, temporal transcriptomics profiling of FVIII-stimulated peripheral blood mononuclear cells (PBMCs) was carried out for HA subjects with and without a current or historic inhibitor using RNA-Seq. PBMCs were isolated from 40 subjects in the following groups: HA with an inhibitor that resolved either following ITI or spontaneously; HA with a current inhibitor; HA with no inhibitor history and non-HA controls. PBMCs were stimulated with 5 nM FVIII and RNA was isolated 4, 16, 24, and 48 h following stimulation. Time-series differential expression analysis was performed and distinct transcriptional signatures were identified for each group, providing clues as to cellular mechanisms leading to or accompanying their disparate anti-FVIII antibody responses. Subjects with a current inhibitor showed differential expression of 56 genes and a clustering analysis identified three major temporal profiles. Interestingly, gene ontology enrichments featured innate immune modulators, including NLRP3, TLR8, IL32, CLEC10A, and COLEC12. NLRP3 and TLR8 are associated with enhanced secretion of the pro-inflammatory cytokines IL-1β and TNFα, while IL32, which has several isoforms, has been associated with both inflammatory and regulatory immune processes. RNA-Seq results were validated by RT-qPCR, ELISAs, multiplex cytokine analysis, and flow cytometry. The inflammatory status of HA patients suffering from an ongoing inhibitor includes up-regulated innate immune modulators, which may act as ongoing danger signals that influence the responses to, and eventual outcomes of, ITI therapy.
Angesichts des kürzlich von der Bundesregierung verabschiedeten Konjunkturpakets, stellen sich die Autoren des Policy Letters die Frage, ob und inwieweit die angekündigte Mehrwertsteuersenkung sowie der Kinderbonus zur substantiellen Ankurbelung des Binnenkonsums führt. Aus den für das Haushaltskrisenbarometer erhobenen Daten zu Einkommensänderungen sowie Einkommens- und Kündigungserwartungen, können die Ökonomen keine zu erwartende Schwächung der Binnennachfrage ableiten. Der überwiegende Teil der deutschen Wohnbevölkerung scheint kurzfristig nicht davon auszugehen, finanzielle Einbußen aufgrund der Pandemie zu erleiden. Die Erwartungen hinsichtlich der künftigen Einkommensentwicklung haben sich gar über die letzten vier Umfragewellen graduell verbessert. Ferner kann dargelegt werden, dass weder die Konsum- noch die Sparneigung durch die Corona-Krise zum gegenwärtigen Zeitpunkt langfristig stark beeinflusst wird. So geben derzeit lediglich 10 Prozent der Befragten an, größere Anschaffungen angesichts der Pandemie vollständig gestrichen zu haben. Anfang April 2020 lag dieser Wert noch bei 16 Prozent. Die Befragten berichteten in 71 Prozent der Fälle ihre Konsumpläne und in 78 Prozent der Fälle ihre Sparverhalten nicht geändert zu haben. Im Lichte dieser Ergebnisse lassen sich Maßnahmen, die auf eine unspezifische Stimulierung der Binnennachfrage abzielen, nicht substantiell begründen und rechtfertigen.