L’ambito della storia della sicurezza è cresciuto rapidamente negli anni recenti – nonostante appaia ancora quello meno indagato all’interno dell’ampio contesto interdisciplinare degli studi sulla sicurezza. L’articolo cerca di disegnare un schizzo dello stato dell’arte, sottolineando tre aspetti: in primo luogo, una (tuttora assente) storia della sicurezza di età rinascimentale – la storia dell’iniziale concetto di sicurezza collettiva transterritoriale sviluppato nell’ambito del sistema degli Stati italiani del Quattrocento; in secondo luogo, lo sviluppo della sicurezza come principio guida dell’amministrazione interna allo Stato soprattutto nell’Europa continentale nei secoli XVII e XVIII; in terzo luogo, le sfide di una storia della sicurezza ambientale come storia delle relazioni transterritoriali e transnazionali tra economie politiche, natura e volontà di fornire sicurezza (a esseri umani, Stati, imperi).View less
Das „Modell Deutschland“ hat sich in der Vergangenheit als überaus stabil erwiesen. Gleichwohl steht aktuell die Automobilindustrie, die zentrale Branche des deutschen Kapitalismusmodells, vor tief greifenden Transformationen, deren genaue Konturen sich jedoch nur erahnen lassen. Der Beitrag diskutiert aus einer regulationstheoretischen Perspektive die sich abzeichnenden Veränderungen und argumentiert, dass die internationale Einbettung des „Modell Deutschland“ nicht nur im Hinblick auf die aktuelle Doppelkrise des liberalen Kapitalismus, sondern auch im Hinblick auf die materiell-stoffliche Dimension des deutschen Exportmodells von zentraler Bedeutung ist. Darüber hinaus bedarf es eines präziseren Verständnisses der Rekonfiguration der automobilen Wertschöpfungsketten, die sich durch Digitalisierung und neue Mobilitätsdienstleistungen sowie eine Veränderung der Rohstoffbedarfe und industrieller Fertigungsprozesse im Zuge der Elektrifizierung des Antriebsstrangs verändern und sowohl das Lohnverhältnis als auch die Unternehmensformen stark beeinflussen.View less
Medicinal mushrooms are widely used in East Asia for the treatment of various diseases, especially in complementary cancer care. While there is a growing interest in medicinal mushrooms in Western countries and an increasing number of pre-clinical studies indicate distinct anti-cancer and regenerative properties, little is known about their potential relevance for clinical practice. This review aims to provide an overview of the clinical evidence, significance and potential role of medicinal mushrooms in complementary cancer care. Scientific databases for (randomized) controlled clinical trials evaluating whole spectrum formulations of medicinal mushrooms (mushroom powder and mushroom extracts) in cancer patients during and/or after conventional oncological treatment were searched. Eight studies met our inclusion criteria (eight randomized controlled trials, one controlled clinical trial). The medicinal mushrooms investigated were Agaricus sylvaticus (two trials), Agaricus blazei murill (two trials), Antrodia cinnamomea (one trial), Coriolus versicolor (one trial) and Ganoderma lucidum (three trials); all were compared to placebo and administered orally. A variety of cancer entities, outcomes and treatment durations were observed. Study results suggested beneficial effects of medicinal mushrooms, particularly quality of life and reduction of adverse effects of conventional therapies. Also, positive effects on antitumor activity and immunomodulation were reported, e.g., an increased activity of natural killer cells. In addition, results might suggest a longer survival of cancer patients receiving mushroom preparations, although in most studies this was not significant when compared to placebo. Adverse events of treatment with medicinal mushrooms were poorly reported; gastrointestinal reactions and a decrease in platelet cell count occurred in some cases. The methodological quality of most studies was generally unsatisfying and most results were insufficiently reported in several respects. Medicinal mushrooms may have a therapeutic potential for cancer patients during and after conventional oncological care with regards to quality of life, reduction of adverse effects of conventional care and possibly other surrogate parameters like immune function. There is an urgent need to investigate the safety and possible interactions of medicinal mushrooms. High-quality clinical research is warranted in order to clarify the potential of medicinal mushrooms in cancer therapy.View less
Background: In pemphigus, elucidating the disease-causing immune mechanism and developing new therapeutic strategies are needed. In this context, the second messenger 3',5'-cyclic adenosine monophosphate (cAMP) is gaining attention. cAMP is important in hematological and auto-inflammatory disorders. A class of enzymes called phosphodiesterases (PDEs) control intracellular cAMP levels. In pemphigus, cAMP levels increase following IgG binding to Dsg3. This appears to be a mechanism to preserve epithelial integrity.
Objectives: To determine whether apremilast, an inhibitor of the PDE4 normally used in psoriasis, may be of benefit in the blistering skin disorder pemphigus.
Methods: Here we report of a 62 years old patient with chronic debilitating and recalcitrant pemphigus not responding to several previous treatments, who received treatment with apremilast over a period of 32 weeks. Desmoglein autoantibody levels were assessed by Enzyme-linked Immunosorbent Assay (ELISA), whereas disease severity and quality of life were assessed by the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). In an attempt to explain the effects of apremilast in pemphigus, peripheral blood mononuclear cells (PBMCs) were analyzed for the duration of treatment by flow cytometry for the distribution of specialized T cell subsets. The frequencies of circulating T helper (Th) 1, Th2, Th17, Th17.1 and T follicular helper (Tfh) 1, Tfh2, Tfh17, and Tfh17.1 were analyzed by CCR6, CXCR3, and CXCR5 expression of CD4(+) T cells. Further, based on the different expressions of CXCR5, CD127, and CD25, we analyzed the T regulatory (Treg) and T follicular regulatory (Tfreg) compartment.
Results: In response to apremilast treatment, Dsg-specific autoantibody titers decreased, blistering ceased and lesions healed, showing a long-lasting effect. While the frequencies of most of the Th and Tfh cell subsets remained unchanged, we observed a continuous increase in Treg and Tfreg cell levels.
Conclusion: Our findings are encouraging and warrant extension of the beneficial effect of PDE4 inhibition on a larger cohort of pemphigus patients.View less
Die COVID-19-Pandemie perturbiert alle gesellschaftlichen Sektoren und führt eindrücklich vor Augen, dass sie miteinander verwoben sind. Dieser Prozess lässt sich gut als Verhältnis von Resilienz und Vulnerabilität der Teilsysteme begreifen. Aus aktuellen human ökologischen Diskursen mit systemtheoretischem Fokus leiten wir zwei Rahmenmodel le zum Struktur- und Prozessverständnis der Pandemie und ihrer Effekte ab und stellen sie hier zur Diskussion.View less
Due to growing global socio-economic and environmental challenges (population ageing, climate change, society polarization, etc.), there is a revaluation of a position and role of innovations in overcoming threats to social development in the modern world. Researchers note a shift in the innovation paradigm toward social innovation, since it is assumed that it is not possible to achieve a drastic improvement of the situation solely through technological innovations. At the same time, many existing problems cannot be solved with efforts of a single actor - intersectoral cooperation becomes a necessity. This aspect is of key importance for development of social innovation. The purpose of the study was to analyze development of social innovations in the Russian Federation based on an actor approach, which involves an overview of this phenomenon through the prism of activities of various entities and their interaction. General scientific methods were used in the study: discourse analysis, generalization, comparison, etc. Essential foundations and the role of social innovations in solving current society's problems are presented. Using the example of government structures, big business, and civil society, the authors explore the features of social innovation development in Russia. It is shown that development of social innovations depends on their interpretation in public discourse, involvement in strategies of various actors, and intersectoral cooperation in the innovation process. In conclusion, the prospects for development of studied phenomenon are determined within identified trends and the specifics of interconnections between designated actors. The results obtained may be used not only as an empirical basis for further research, but they may also represent practical significance in development of specific management decisions in this area.View less
Rifampin plays a crucial role in the treatment of staphylococcal implant-associated infection, as it is the only antibiotic capable of eradicating Staphylococcus aureus biofilms. However, the emergence of rifampin resistance strongly limits its use. Combinatorial therapy of antibiotics and bacteriophages may represent a strategy to overcome the resistance. Here, we evaluated the activity of staphylococcal bacteriophage Sb-1 in combination with different antibiotics against the biofilms of 10 rifampin-resistant S. aureus clinical strains, including MRSA and MSSA. S. aureus biofilms formed on porous glass beads were exposed to antibiotics alone or combined with Sb-1 simultaneously or staggered (first Sb-1 for 24 h followed by antibiotic). Recovered bacteria were detected by measuring growth-related heat production at 37°C (isothermal microcalorimetry) and the biofilm eradication was assessed by sonication of beads and plating of the resulting sonication fluid. Minimum biofilm eradication concentration (MBEC) was defined as the lowest concentration of antibiotic required to kill all adherent bacteria, resulting in absence of growth after plating the sonication fluid. Tested antibiotics presented high MBEC values when administered alone (64 to > 1,024 μg/ml). The simultaneous or staggered combination of Sb-1 with daptomycin showed the highest activity against all MRSA biofilms, whereas the exposure to Sb-1 with vancomycin showed no improved anti-biofilm activity. Staggered administration of Sb-1 and flucloxacillin, cefazolin, or fosfomycin improved the antibiofilm activity in four out of six MSSA, whereas simultaneous exposure exhibited similar or lesser synergy. In conclusion, the combinatorial effect of Sb-1 and antibiotics enabled to eradicate rifampin-resistant S. aureus biofilms in vitro.View less
This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.View less
Light is important for plants as an energy source and a developmental signal, but it can also cause stress to plants and modulates responses to stress. Excess and fluctuating light result in photoinhibition and reactive oxygen species (ROS) accumulation around photosystems II and I, respectively. Ultraviolet light causes photodamage to DNA and a prolongation of the light period initiates the photoperiod stress syndrome. Changes in light quality and quantity, as well as in light duration are also key factors impacting the outcome of diverse abiotic and biotic stresses. Short day or shady environments enhance thermotolerance and increase cold acclimation. Similarly, shade conditions improve drought stress tolerance in plants. Additionally, the light environment affects the plants' responses to biotic intruders, such as pathogens or insect herbivores, often reducing growth‐defence trade‐offs. Understanding how plants use light information to modulate stress responses will support breeding strategies to enhance crop stress resilience. This review summarizes the effect of light as a stressor and the impact of the light environment on abiotic and biotic stress responses. There is a special focus on the role of the different light receptors and the crosstalk between light signalling and stress response pathways.View less
Karst aquifers are abundant, but vulnerable water resources. Therefore, a deeper understanding of possible mechanisms that determine the properties of karst springs is crucial. In this work, we present an example of Unica Spring and Malni Spring, the two main outlets of a large karst system in the Notranjska karst region, Slovenia. Although the two springs share same catchment area, the flow distribution between them shows an interesting behaviour: At low-flow conditions Malni Spring is the main outlet, while Unica spring receives almost no water. During high water events, discharge of Malni Spring stays limited and Unica Spring becomes the main outlet. We relate these observations to the local geometry of the channels and breakdowns in the remote part of the Planinska Jama (Planina Cave), called Mysterious Lake. There, waters from Rakov kocjan and Javorniki aquifer merge and further diverge to both springs. At low water conditions, the outflow towards the Unica Spring is restricted by the breakdown, so that most of the inflow is directed towards the Malni Spring. With increasing recharge, the level in Mysterious Lake rises until the water starts to flow over the breakdown along a system of large channels (Rak Branch of Planinska Jama) to the Unica Spring. The breakdown level keeps the hydraulic head and the flow towards Malni Spring limited. To verify this scenario, a hydraulic conduit model was made based on the known and predicted channels, and inflows calculated from the historical data of discharge measurements at related springs and ponors. An inversion procedure was used to obtain a satisfactory fit to the observed discharge data and to constrain the selected model parameters. The model accurately reproduced the observed discharge behaviour under low- and high-flow conditions.View less
The sharing economy has brought new opportunities to the logistics industry, which has created an emerging trend known as crowd logistics. Implementing this mode offers a basis for more sustainable urban logistics, but there is limited research on what leads enterprises to adopt crowd logistics. Based on the technology-organization-environment (TOE) theoretical model, this paper developed a model to study the influencing factors of enterprises' willingness to implement crowd logistics. The data were collected through questionnaire surveys, SPSS and AMOS were used for data analysis. The empirical results showed that the relative advantage, absorptive capacity, market environment, and external motivations have significant positive impact on the company's willingness to implement crowd logistics, while complexity and resources have no significant impact. Crowd logistics offers an important route to more sustainable urban logistics. Logistics enterprises should take measured steps when implementing crowd logistics, improve their absorptive capacity, and take necessary precautions towards minimizing the risks of crowd logistics.View less
The 1s(-2) Auger hypersatellite spectrum of argon is studied experimentally and theoretically. In total, three transitions to the final states 1s(-1)2p(-2)(S-2(e),D-2(e)) and 1s(-1)2s(-1)(S-1)2p(-1)(P-2(o)) are experimentally observed. The lifetime broadening of the 1s(-2) -> 1s(-1)2p(-2)(S-2(e),D-2(e)) states is determined to be 2.1(4) eV. For the used photon energy of h nu = 7500 eV a KK/K ionisation ratio of 2.5(3) x 10(-4) is derived. Generally, a good agreement between the experimental and present theoretical energy positions, linewidths, and intensities is obtained.View less
Although heart failure following myocardial infarction (MI) represents a major health burden, underlying microstructural and functional changes remain incompletely understood. Here, we report on a case of unexpected MI after treatment with the catecholamine isoproterenol in an experimental imaging study in mice using different state-of-the-art imaging modalities. The decline in cardiac function was documented by ultrahigh-frequency echocardiography and speckle-tracking analyses. Myocardial microstructure was studied ex vivo at a spatial resolution of 100 x 100 x 100 mu m(3) using diffusion tensor magnetic resonance imaging (DT-MRI) and histopathologic analyses. Two weeks after ISO treatment, the animal showed an apical aneurysm accompanied by reduced radial strain in corresponding segments and impaired global systolic function. DT-MRI revealed a loss of contractile fiber tracts together with a disarray of remaining fibers as corresponding microstructural correlates. This preclinical case report provides valuable insights into pathophysiology and morphologic-functional relations of heart failure following MI using emerging imaging technologies.View less
Spin chains with symmetry-protected edge modes are promising candidates to realize intrinsically robust physical qubits that can be used for the storage and processing of quantum information. In any experimental realization of such physical systems, weak perturbations in the form of induced interactions and disorder are unavoidable and can be detrimental to the stored information. At the same time, the latter may in fact be beneficial; for instance, by deliberately inducing disorder which causes the system to localize. We explore the potential of using an XZX cluster Hamiltonian to encode quantum information into the local edge modes and comprehensively investigate the influence of both many-body interactions and disorder on their stability over time, adding substance to the narrative that many-body localization may stabilize quantum information. We recover the edge state at each time step, allowing us to reconstruct the quantum channel that captures the locally constrained out-of-equilibrium time evolution. With this representation in hand, we analyze how well classical and quantum information are preserved over time as a function of disorder and interactions. We find that the performance of the edge qubits varies dramatically between disorder realizations. Whereas some show a smooth decoherence over time, a sizable fraction is rapidly rendered unusable as memories. We also find that the stability of the classical information-a precursor for the usefulness of the chain as a quantum memory-depends strongly on the direction in which the bit is encoded. When employing the chain as a genuine quantum memory, encoded qubits are most faithfully recovered for low interaction and high disorder.View less
In Gaussian quantum key distribution eavesdropping attacks are conventionally modeled through the universal entangling cloner scheme, which is based on the premise that the whole environment is under control of the adversary, i.e., the eavesdropper purifies the system. This assumption implies that the eavesdropper has either access to an identity (noiseless) channel or an infinite amount of entanglement in order to simulate such an identity channel. In this work we challenge the necessity of this assumption and we propose a teleportation-based eavesdropping attack, where the eavesdropper is not assumed to have access to the shared channel, that represents the unavoidable noise due to the environment. Under collective measurements, this attack reaches optimality in the limit of an infinite amount of entanglement, while for finite entanglement resources it outperforms the corresponding optimal individual attack. We also calculate the minimum amount of distributed entanglement that is necessary for this eavesdropping scheme, since we consider it as the operationally critical quantity capturing the limitations of a realistic attack. We conclude that the fact that an infinite amount of entanglement is required for an optimal collective eavesdropping attack signifies the robustness of Gaussian quantum key distribution.View less
All around the world, intestinal helminths constitute one of the most prevalent life-long occurring infections and re-infections affecting all horse age groups. A range of parasite species among strongyles, ascarids, and tapeworms is known to have the potential to cause colic in horses. However, there is a lack of current scientific evidence on the actual relevance of helminth infection levels in the context of colic in horses kept during prevailing epidemiological conditions. Thus, a prospective case-control study on the occurrence of intestinal helminths in a total of 620 mainly adult equine clinic patients was conducted to investigate the association between colic and helminth infection. For each horse, a range of copromicroscopic, serological, and clinical data was obtained, in addition to a questionnaire on relevant anamnestic data, including previous anthelmintic treatment and husbandry. Using a FLOTAC-based copromicroscopic diagnosis, the highest infection rates were seen for strongyles (41.8%), followed by Anoplocephala perfoliata and Parascaris spp. (both 0.8%), with no significant difference between the two study groups. Employing a real-time PCR a 1.1% S. vulgaris DNA prevalence was found. Considerably higher seroprevalences were observed using S. vulgaris and A. perfoliata ELISAs, with 32.3% and 10.7%, respectively. It was noteworthy that no association concerning either serologic status was encountered with colic status. The shedding of strongyle eggs was associated with a 1.8-times increased risk of S. vulgaris seropositivity. Recent anthelmintic treatment was associated with the onset of colic, as animals who had received an anthelmintic during the previous week had a 2.4-times higher risk of signs of colic compared to those who had been treated at least eight weeks prior. Another noteworthy observation was that ponies were significantly less often affected by colic than warmbloods. The high S. vulgaris and considerable A. perfoliata seroprevalences encountered in this investigation should prompt veterinarians, farm managers, and horse owners to maintain consequent and effective worm control measures.View less
The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales (Col-E), as well as vancomycin-resistant enterococci (VRE). In total, 505 samples from four stages of meat production, i.e., slaughterhouses, meat-processing plants, fresh food products and the urban environment, were collected in northwestern Germany in 2018/2019 and screened for the presence of MDRB using both culture-based and PCR-based techniques. We detected genes encoding for carbapenemases in 9–56% (blaOXA-48, blaKPC, blaNDM, blaVIM) and colistin resistance-encoding mcr genes in 9–26% of the samples from all stages. Culture-based analysis found CPE and VRE only in environmental samples (11% and 7%, respectively), but Col-E and ESBL-producers in 1–7% and 12–46% of samples from all stages, respectively. Overall, our results showed that ESBL-producers and mcr-carrying Col-E were common in food-producing animals at slaughterhouses, in meat-processing plants and in food items at retail, while CPE and VRE were only found in the environment. The discrepancy between detected carbapenemase genes and isolated CPE emphasizes the need for more sensitive detection methods for CPE monitoring.View less
Human cytomegalovirus (HCMV) is a human pathogenic herpesvirus associated with a variety of clinical symptoms. Current antiviral therapy is not always effective, so that improved drug classes and drug-targeting strategies are needed. Particularly host-directed antivirals, including pharmaceutical kinase inhibitors (PKIs), may help to overcome problems of drug resistance. Here, we focused on utilizing a selection of clinically relevant PKIs and determined their anticytomegaloviral efficacies. Particularly, PKIs directed to host or viral cyclin-dependent kinases, i.e., abemaciclib, LDC4297 and maribavir, exerted promising profiles against human and murine cytomegaloviruses. The anti-HCMV in vitro activity of the approved anti-cancer drug abemaciclib was confirmed in vivo using our luciferase-based murine cytomegalovirus (MCMV) animal model in immunocompetent mice. To assess drug combinations, we applied the Bliss independence checkerboard and Loewe additivity fixed-dose assays in parallel. Results revealed that (i) both affirmative approaches provided valuable information on anti-CMV drug efficacies and interactions, (ii) the analyzed combinations comprised additive, synergistic or antagonistic drug interactions consistent with the drugs’ antiviral mode-of-action, (iii) the selected PKIs, especially LDC4297, showed promising inhibitory profiles, not only against HCMV but also other α-, β- and γ-herpesviruses, and specifically, (iv) the combination treatment with LDC4297 and maribavir revealed a strong synergism against HCMV, which might open doors towards novel clinical options in the near future. Taken together, this study highlights the potential of therapeutic drug combinations of current developmental/preclinical PKIs.View less