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result(s) for
"Graf, Philipp"
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Twice Exiled
2021
Beginning with an encounter between Erich Honecker and the Jewish communist Leo Zuckermann that took place in Mexico City in September 1981, this article investigates the relationship of the communist movement in the German-speaking world to the ‘Jewish question’ and the Holocaust. At a reception of the GDR embassy on the occasion of Honecker’s state visit, the Chairman of the State Council shook hands with Zuckermann, a formerly high-ranking Socialist Unity Party of Germany functionary who had fled the German Democratic Republic (GDR) in 1952, and assured him that he was happy to see him again. This gesture by Honecker rehabilitated a man over whom a blanket of silence had been spread in the GDR decades earlier: during his first exile in Mexico, Zuckermann had developed positions that granted the Jewish people in light of the crimes of National Socialism the right both to restitution and to an independent state. This article offers new insights into the genesis of Zuckermann’s thinking and illuminates the reactions of the party leadership, which was surprisingly not opposed to such partisanship on behalf of the Jewish collective during a short ‘interim period’ from 1943/4 to 1948/9.
Journal Article
Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro
by
Graf, Philipp
,
Auth, Janina
,
Grassauer, Andreas
in
Animals
,
Antibodies
,
Antibodies, Viral - immunology
2021
In the absence of a vaccine and other effective prophylactic or therapeutic countermeasures the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) remains a significant public health threat. Attachment and entry of coronaviruses including SARS-CoV-2 is mainly mediated by the spike glycoprotein. Here, we show that iota-carrageenan can inhibit the cell entry of the SARS-CoV-2 spike pseudotyped lentivirus in a dose dependent manner. SARS-CoV-2 spike pseudotyped lentivirus particles were efficiently neutralized with an IC 50 value of 2.6 μg/ml iota-carrageenan. Experiments with patient isolated wild type SARS-CoV-2 virus showed an inhibition of replication in a similar range. In vitro data on iota-carrageenan against various Rhino- and endemic Coronaviruses showed similar IC 50 values and translated readily into clinical effectiveness when a nasal spray containing iota-carrageenan demonstrated a reduction of severity and duration of symptoms of common cold caused by various respiratory viruses. Accordingly, our in vitro data on SARS-CoV-2 spike pseudotyped lentivirus and replication competent SARS-CoV-2 suggest that administration of iota-carrageenan may be an effective and safe prophylaxis or treatment for SARS-CoV-2 infections.
Journal Article
The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model
by
Graf, Philipp
,
Grassauer, Andreas
,
Koller, Christiane
in
Administration, Intranasal
,
Animal models
,
Animals
2015
Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo.
We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection.
A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.
Journal Article
Iota-Carrageenan Is a Potent Inhibitor of Influenza A Virus Infection
by
Leibbrandt, Andreas
,
Graf, Philipp
,
Pflugfelder, Bettina
in
Analysis
,
Animals
,
Antiviral Agents - pharmacology
2010
The 2009 flu pandemic and the appearance of oseltamivir-resistant H1N1 influenza strains highlight the need for treatment alternatives. One such option is the creation of a protective physical barrier in the nasal cavity. In vitro tests demonstrated that iota-carrageenan is a potent inhibitor of influenza A virus infection, most importantly also of pandemic H1N1/2009 in vitro. Consequently, we tested a commercially available nasal spray containing iota-carrageenan in an influenza A mouse infection model. Treatment of mice infected with a lethal dose of influenza A PR8/34 H1N1 virus with iota-carrageenan starting up to 48 hours post infection resulted in a strong protection of mice similar to mice treated with oseltamivir. Since alternative treatment options for influenza are rare, we conclude that the nasal spray containing iota-carrageenan is an alternative to neuraminidase inhibitors and should be tested for prevention and treatment of influenza A in clinical trials in humans.
Journal Article
Sociological and Biological Insights on How to Prevent the Reduction in Cognitive Activity that Stems from Robots Assuming Workloads in Human–Robot Cooperation
by
Graf, Philipp
,
Compagna, Diego
,
Weidemann, Alexandra
in
Biology
,
breaching experiments
,
Cognition
2016
The reduction of cognitive tasks brought about by new developments in service-robots’ collaboration with humans in working environments has given rise to new challenges as to how to address safety issues. This paper presents insights from biology, cognitive/neural sciences and sociology that can conquer these new challenges. The main focus lies in sociological variables that ensure safe human–robot interaction in working environments rather than addressing biological ones (avoiding bodily harm) or purely cognitive ones (avoiding any signals that are outside the human’s sensory comfort zones). We will present an approach on how to integrate behavioral patterns into the robotic system in order to prevent the problem of reduced cognition in relation to essential features, which are necessary for carrying out this pattern in the context of a human–robot interaction with non-humanoid robots (which is the most typical design of robots used in work environments).
Journal Article
Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta
by
Auth, Janina
,
Graf, Philipp
,
Fröba, Maria
in
Animals
,
Antiviral Agents - pharmacology
,
Antiviral drugs
2021
The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity. Hence, the need of effective and viable prevention options to reduce viral transmission is of outmost importance. In this study, we investigated the antiviral effect of iota-, lambda- and kappa-carrageenan, sulfated polysaccharides extracted from red seaweed, on SARS-CoV-2 Wuhan type and the spreading variants of concern (VOCs) Alpha, Beta, Gamma and Delta. Carrageenans as part of broadly used nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. Here, we demonstrate by using a SARS-CoV-2 spike pseudotyped lentivirus particles (SSPL) system and patient-isolated SARS-CoV-2 VOCs to infect transgenic A549ACE2/TMPRSS2 and Calu-3 human lung cells that all three carrageenan types exert antiviral activity. Iota-carrageenan exhibits antiviral activity with comparable IC50 values against the SARS-CoV-2 Wuhan type and the VOCs. Altogether, these results indicate that iota-carrageenan might be effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants.
Journal Article
Lectin from Triticum vulgaris (WGA) Inhibits Infection with SARS-CoV-2 and Its Variants of Concern Alpha and Beta
by
Auth, Janina
,
Graf, Philipp
,
Dolischka, Andrea
in
Animals
,
Antiviral Agents - chemistry
,
Antiviral Agents - pharmacology
2021
Even in the face of global vaccination campaigns, there is still an urgent need for effective antivirals against SARS-CoV-2 and its rapidly spreading variants. Several natural compounds show potential as antiviral substances and have the advantages of broad availabilities and large therapeutic windows. Here, we report that lectin from Triticum vulgaris (Wheat Germ Agglutinin) displays antiviral activity against SARS-CoV-2 and its major Variants of Concern (VoC), Alpha and Beta. In Vero B4 cells, WGA potently inhibits SARS-CoV-2 infection with an IC50 of <10 ng/mL. WGA is effective upon preincubation with the virus or when added during infection. Pull-down assays demonstrate direct binding of WGA to SARS-CoV-2, further strengthening the hypothesis that inhibition of viral entry by neutralizing free virions might be the mode of action behind its antiviral effect. Furthermore, WGA exhibits antiviral activity against human coronavirus OC43, but not against other non-coronaviruses causing respiratory tract infections. Finally, WGA inhibits infection of the lung cell line Calu-3 with wild type and VoC viruses with comparable IC50 values. Altogether, our data indicate that topical administration of WGA might be effective for prophylaxis or treatment of SARS-CoV-2 infections.
Journal Article
MGOUN1 Encodes an Arabidopsis Type IB DNA Topoisomerase Required in Stem Cell Regulation and to Maintain Developmentally Regulated Gene Silencing
2010
Maintenance of stem cells in the Arabidopsis thaliana shoot meristem is regulated by signals from the underlying cells of the organizing center, provided through the transcription factor WUSCHEL (WUS). Here, we report the isolation of several independent mutants of MGOUN1 (MGO1) as genetic suppressors of ectopic WUS activity and enhancers of stem cell defects in hypomorphic wus alleles. mgo1 mutants have previously been reported to result in a delayed progression of meristem cells into differentiating organ primordia (Laufs et al., 1998). Genetic analyses indicate that MGO1 functions together with WUS in stem cell maintenance at all stages of shoot and floral meristems. Synergistic interactions of mgo1 with several chromatin mutants suggest that MGO1 affects gene expression together with chromatin remodeling pathways. In addition, the expression states of developmentally regulated genes are randomly switched in mgo1 in a mitotically inheritable way, indicating that MGO1 stabilizes epigenetic states against stochastically occurring changes. Positional cloning revealed that MGO1 encodes a putative type IB topoisomerase, which in animals and yeast has been shown to be required for regulation of DNA coiling during transcription and replication. The specific developmental defects in mgo1 mutants link topoisomerase IB function in Arabidopsis to stable propagation of developmentally regulated gene expression.
Journal Article
Floor Cleaners as Helper Pets: Projecting Assistive Robots’ Agency on Zoomorphic Affordances
by
Graf, Philipp
,
Grimme, Sophie Alice
,
Kollakidou, Avgi
in
Accessibility and Wellbeing
,
Adults
,
Aging
2023
Care of ageing adults has become a dominant field of application for assistive robot technologies, promising support for ageing adults residing in care homes and staff, in dealing with practical routine tasks and providing social and emotional relieve. A time consuming and human intensive necessity is the maintenance of high hygiene quality in care homes. Robotic vacuum cleaners have been proven effective for doing the job elsewhere, but—in the context of care homes—are counterproductive for residents’ well-being and do not get accepted. This is because people with dementia manifest their agency in more implicit and emotional ways, while making sense of the world around them. Starting from these premises, we explored how a zoomorphic designed vacuum cleaner could better accommodate the sensemaking of people with dementia. Our design reconceptualises robotic vacuum cleaners as a cat-like robot, referring to a playful behaviour and appearance to communicate a non-threatening and familiar role model. Data from an observational study shows that residents responded positively to our prototype, as most of them engaged playfully with it as if it was a pet or a cat-like toy, for example luring it with gestures. Some residents simply ignored the robot, indicating that it was not perceived as frightening or annoying. The level of activity influenced reactions; residents ignored our prototype if busy with other occupations, which proves that it did not cause significant disturbance. We further report results from focus group sessions with formal and informal caregivers who discussed a video prototype of our robot. Caregivers encouraged us to enhance the animal like characteristics (in behaviour and materiality) even further to result in richer interactions and provoke haptic pleasure but also pointed out that residents should not mistake the robot for a real cat.
Journal Article
Decongestant Effect of “Coldamaris Akut”, a Carrageenan- and Sorbitol-Containing Nasal Spray in Seasonal Allergic Rhinitis
by
Graf, Philipp
,
Zieglmayer, René
,
Morokutti-Kurz, Martina
in
Allergens
,
Allergies
,
Antibiotics
2024
This study aimed to develop a hyperosmolar, barrier-forming nasal spray based on carrageenan and sorbitol, and to demonstrate its decongestant effect in the context of allergic rhinitis (AR).
The efficacy of the nasal spray components was tested in vitro by barrier function, virus replication inhibition, and water absorption assays. The decongestant effectiveness was assessed in a randomized, controlled, crossover environmental chamber trial, where participants with a history of seasonal grass pollen AR were exposed to grass pollen allergens under controlled conditions. Forty-one adults were randomized to receive either carrageenan- and sorbitol-containing nasal spray (CS) or saline solution (SS). After 1 week, participants repeated the exposure with the treatment they had not received before. The primary efficacy endpoint was the mean change in nasal congestion symptom score (NCSS). Secondary efficacy endpoints were nasal airflow, nasal secretion, total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total respiratory symptom score (TRSS).
Preclinical assays demonstrated barrier-building, virus-blocking, and water-withdrawing properties of the CS components. In the clinical study, there was no significant difference in mean NCSS change from pre- to post-treatment between CS and SS. However, nasal airflow increased over time after treatment with CS, while it declined after SS, leading to a growing difference in airflow between CS and SS (p = 0.04 at 6:00 h). Mean nasal secretion over 2-6 h was reduced by ~25% after CS (p = 0.003) compared to pre-treatment, while it was reduced by only ~16% after SS (p = 0.137). No significant differences in TNSS, TOSS and TRSS were observed between CS and SS.
CS improves nasal airflow and reduces nasal secretion in adults with AR. We propose CS as a safe and effective adjuvant to baseline pharmacological treatments.
NCT04532762.
Journal Article