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Unexpected Enhancement of Antimicrobial Polymer Activity against Staphylococcus aureus in the Presence of Fetal Bovine Serum
Cationic and amphiphilic polymers are known to exert broad-spectrum antibacterial activity by a putative mechanism of membrane disruption. Typically, nonspecific binding to hydrophobic components of the complex biological milieu, such as globular proteins, is considered a deterrent to the successful application of such polymers. To evaluate the extent to which serum deactivates antibacterial polymethacrylates, we compared their minimum inhibitory concentrations in the presence and absence of fetal bovine serum. Surprisingly, we discovered that the addition of fetal bovine serum (FBS) to the assay media in fact enhances the antimicrobial activity of polymers against Gram-positive bacteria S. aureus, whereas the opposite is the case for Gram-negative E. coli. Here, we present these unexpected trends and develop a hypothesis to potentially explain this unusual phenomenon
ADAR RNA Modifications, the Epitranscriptome and Innate Immunity
Modified bases act as marks on cellular RNAs so that they can be distinguished from foreign RNAs, reducing innate immune responses to endogenous RNA. In humans, mutations giving reduced levels of one base modification, adenosine-to-inosine deamination, cause a viral infection mimic syndrome, a congenital encephalitis with aberrant interferon induction. These Aicardi-Goutieres syndrome 6 mutations affect adenosine deaminase acting on RNA 1 (ADAR1), which generates inosines in endogenous double-stranded (ds)RNA. The inosine base alters dsRNA structure to prevent aberrant activation of antiviral cytosolic helicase RIG-I-like receptors. We review how effects of inosines, ADARs, and other modi-fied bases have been shown to be important in innate immunity and cancer
Evaluate the Level of Dependence,Quality of life, Effectiveness of Nursing Interventions among Cerebral palsy children and the Caregivers Stress burden, Coping strategies in KSA.
Zur Deutung des Lehrberufs durch Lehrer und Lehrerinnen. Eine Geschichte berufsbezogener Deutungsmuster. Projektskizze
Mit dem vorliegenden Papier möchte ich ein Forschungsprojekt in einem frühen Stadium zur Diskussion stellen. Das Ziel meines Vorhabens ist es, berufsbezogene Deutungsmuster und Rollenkonstruktionen bei Lehrern und Lehrerinnen in ihrem historischen Wandel zu untersuchen. Die Frage, um welche die hier gemeinten Deutungsmuster kreisen, ist simpel und folgenschwer zugleich: „Warum bin ich eigentlich Lehrer?“ – „Warum bin ich eigentlich Lehrerin?“. Es geht also primär nicht um Deutungsmuster in Bezug auf Probleme und Herausforderungen, die sich im konkreten Berufsalltag stellen (wie z.B. Umgang mit Unterrichtsstörungen, Austarieren von Nähe und Distanz im Verhältnis zu Lernenden usw.), obwohl solche Probleme natürlich in die hier zu bearbeitende Frage hineinspielen können. Im Fokus steht vielmehr die Frage, wie Lehrerinnen und Lehrer den eigenen Beruf insgesamt auffassten, und welche Bedeutung der Lehrberuf für sie im Hinblick auf die Konstruktion von Lebenssinn hatte. Wie der Sinnhorizont, der die Ebene des konkreten Handelns im Berufsalltag überwölbt, im Einzelnen konstruiert war, variierte und variiert zweifelsohne zwischen einzelnen Individuen. Derartige Deutungsmuster werden aber auch kommunikativ vermittelt und von Individuen im Sozialisationsprozess angeeignet, so dass man davon ausgehen kann, dass es Deutungsmuster gibt, die für eine Gesellschaft bzw. eine bestimmte soziale Gruppe innerhalb einer Gesellschaft in ihrer jeweiligen historischen Verfasstheit spezifisch sind. Deutungen in Bezug auf den Sinn des Berufs, die beruflichen Aufgaben und auf die Rolle des Berufes in der Gesellschaft standen in engem Zusammenhang mit dem beruflichen Engagement von Lehrerinnen und Lehrern. Bei beruflichem Engagement ist an unterschiedliche Aspekte zu denken. An erster Stelle ist wohl die konkrete Arbeit im Klassenzimmer, also das Unterrichtshandeln zu nennen. Auch wenn das der Ort ist, wo sich Lehrerhandeln zum überwiegenden Teil vollzieht, sollen im Zentrum dieses Projekts zwei andere Aspekte stehen, die näher an der Frage nach dem Zusammenhang Lehrberuf und Lebenssinn angesiedelt sind. Der erste betrifft die Möglichkeit, das eigene Tätigkeitsfeld nachhaltig und über das eigene Wirken im Unterricht hinaus zu verbessern: die Mitwirkungen an Schulreform bzw. Schulentwicklung. Der zweite betrifft die Frage, wie man den eigenen Wirkungskreis, also die Schule, zur Frage der Gestaltung gesellschaftlicher Verhältnisse insgesamt in Relation setzt, und lässt sich mit dem Schlagwort Schule und Politik überschreiben. Der historische Wandel solcher Deutungsmuster also soll im hier vorgestellten Projekt detaillierter untersucht werden: Welche Muster der Deutung des Verhältnisses zwischen Beruf und Lebenssinn lassen sich historisch ausmachen; welche Muster der Deutung der eigenen Berufsrolle und der sozialen Bedeutung des eigenen Berufes? Wie haben sich diese im Zeitverlauf verändert, wie hingen Veränderungen mit dem Wandel der sozialen Lage von Lehrerinnen und Lehrer einerseits, mit dem Wandel außerpädagogischer Diskurse anderseits zusammen und welche Wechselwirkungen bestanden zwischen solchen in der Sphäre des Ideellen zu verortenden Bildern und konkreten Haltungen in Bezug auf beruflichen Aufgaben? Der Zeitraum, auf den sich eine solche Fragestellung sinnvollerweise beziehen kann, beginnt mit der flächendeckenden Etablierung eines staatlich gesteuerten Schulwesens im späten 18. und frühen 19. Jahrhundert, mit der sich der Lehrberuf sowohl an höheren als auch an niederen Schulen als eigenständiger Beruf im modernen Sinn konstituierte, und erstreckt sich bis in die Gegenwart. Aus arbeitsökonomischen Erwägungen wird sich die Untersuchung auf die Verhältnisse in Deutschland und Österreich beschränken.Übersetzungstypen Textübersetzung Ausgangstext 3.753 / 5.000 Übersetzungsergebnisse With this paper, I would like to put a research project up for discussion at an early stage. The goal of my project is to examine job-related interpretation patterns and role constructions among teachers in their historical change. The question around which the interpretation patterns meant here revolve is simple and at the same time momentous: "Why am I actually a teacher?" - "Why am I actually a teacher?". It is therefore not primarily about patterns of interpretation in relation to problems and challenges that arise in concrete everyday work (such as dealing with disruptions in class, balancing of closeness and distance in relation to learners, etc.), although such problems are of course part of the question to be dealt with here can play into. Rather, the focus is on the question of how teachers perceive their own profession as a whole and what significance the teaching profession had for them with regard to the construction of meaning in life. How the horizon of meaning, which overarches the level of concrete action in everyday working life, was constructed in detail, undoubtedly varied and varies between individuals. However, such patterns of interpretation are also conveyed communicatively and adopted by individuals in the socialization process, so that one can assume that there are patterns of interpretation that are specific to a society or a certain social group within a society in its respective historical constitution. Interpretations of the meaning of the profession, the professional tasks and the role of the profession in society were closely related to the professional commitment of teachers. When it comes to professional engagement, different aspects have to be considered. First and foremost is the concrete work in the classroom, i.e. the teaching activity. Even if this is the place where most of the teaching takes place, this project should focus on two other aspects that are closer to the question of the relationship between the teaching profession and the meaning of life. The first relates to the possibility of improving one's own field of activity in the long term and beyond one's own work in the classroom: participation in school reform or school development. The second concerns the question of how one relates one's own sphere of activity, i.e. the school, to the question of shaping social conditions as a whole, and can be overwritten with the catchphrase school and politics. The historical change of such interpretation patterns is to be examined in more detail in the project presented here: Which patterns of the interpretation of the relationship between profession and meaning of life can be identified historically; which patterns of interpretation of one's own professional role and the social significance of one's own profession? How have these changed over time, how are changes related to the change in the social situation of teachers on the one hand, and to the change in non-educational discourses on the other hand, and what interactions existed between such images, which are to be located in the sphere of the ideal, and concrete attitudes in relation to professional duties? The period to which such a question can meaningfully refer begins with the nationwide establishment of a state-controlled school system in the late 18th and early 19th centuries, with which the teaching profession at both higher and lower schools developed as an independent profession in modern Sense constituted, and extends to the present. Due to economic considerations, the study will be limited to the situation in Germany and Austria
Di-ANFIS: an integrated blockchain–IoT–big data-enabled framework for evaluating service supply chain performance
Service supply chain management is a complex process because of its intangibility, high diversity of services, trustless settings, and uncertain conditions. However, the traditional evaluating models mostly consider the historical performance data and fail to predict and diagnose the problems’ root. This paper proposes a distributed, trustworthy, tamper-proof, and learning framework for evaluating service supply chain performance based on Blockchain and Adaptive Network-based Fuzzy Inference Systems (ANFIS) techniques, named Di-ANFIS. The main objectives of this research are: 1) presenting hierarchical criteria of service supply chain performance to cope with the diagnosis of the problems’ root; 2) proposing a smart learning model to deal with the uncertainty conditions by a combination of neural network and fuzzy logic, 3) and introducing a distributed Blockchain-based framework due to the dependence of ANFIS on big data and the lack of trust and security in the supply chain. Furthermore, the proposed six-layer conceptual framework consists of the data layer, connection layer, Blockchain layer, smart layer, ANFIS layer, and application layer. This architecture creates a performance management system using the Internet of Things (IoT), smart contracts, and ANFIS based on the Blockchain platform. The Di-ANFIS model provides a performance evaluation system without needing a third party and a reliable intermediary that provides an agile and diagnostic model in a smart and learning process. It also saves computing time and speeds up information flow.Service supply chain management is a complex process because of its intangibility, high diversity of services, trustless settings, and uncertain conditions. However, the traditional evaluating models mostly consider the historical performance data and fail to predict and diagnose the problems’ root. This paper proposes a distributed, trustworthy, tamper-proof, and learning framework for evaluating service supply chain performance based on Blockchain and Adaptive Network-based Fuzzy Inference Systems (ANFIS) techniques, named Di-ANFIS. The main objectives of this research are: 1) presenting hierarchical criteria of service supply chain performance to cope with the diagnosis of the problems’ root; 2) proposing a smart learning model to deal with the uncertainty conditions by a combination of neural network and fuzzy logic, 3) and introducing a distributed Blockchain-based framework due to the dependence of ANFIS on big data and the lack of trust and security in the supply chain. Furthermore, the proposed six-layer conceptual framework consists of the data layer, connection layer, Blockchain layer, smart layer, ANFIS layer, and application layer. This architecture creates a performance management system using the Internet of Things (IoT), smart contracts, and ANFIS based on the Blockchain platform. The Di-ANFIS model provides a performance evaluation system without needing a third party and a reliable intermediary that provides an agile and diagnostic model in a smart and learning process. It also saves computing time and speeds up information flow
Enriching DNS Flows with Host-Based Events to Bypass Future Protocol Encryption
Monitoring of host-based events and network flows are the two most common techniques for collecting and analyzing cybersecurity data. However, events and flows are either monitored separately or correlated as alerts in higher aggregated forms. The event-flow correlation on the monitoring level would match related events and flows together and enabled observing both data in near real-time. This approach allows substituting application-level flow information that will not be available due to encryption, which is being employed in a number of communication protocols. In this paper, we performed the event-flow correlation of the DNS protocol. We developed a general model that describes the relation between events and flows to enable an accurate time-based correlation where parameter-based correlation is not feasible. Based on the model, we designed three event-flow correlation methods based on common parameters and times of occurrence. We evaluated the correlation methods using a recent and public dataset, both with and without the extended flow information, to simulate DNS flow encryption. The results of the method combining parameter-based and time-based matching show that matching related DNS events to flows is possible and substitutes the data that might soon be lost in encryption
GRANEF: Utilization of a Graph Database for Network Forensics
Understanding the information in captured network traffic, extracting the necessary data, and performing incident investigations are principal tasks of network forensics. The analysis of such data is typically performed by tools allowing manual browsing, filtering, and aggregation or tools based on statistical analyses and visualizations facilitating data comprehension. However, the human brain is used to perceiving the data in associations, which these tools can provide only in a limited form. We introduce a GRANEF toolkit that demonstrates a new approach to exploratory network data analysis based on associations stored in a graph database. In this article, we describe data transformation principles, utilization of a scalable graph database, and data analysis techniques. We then discuss and evaluate our proposed approach using a realistic dataset. Although we are at the beginning of our research, the current results show the great potential of association-based analysis
Reinforcing Cybersecurity Hands-on Training With Adaptive Learning
This Research To Practice Full Paper presents how learning experience influences students' capability to learn and their motivation for further learning. Although each student is different, standard instruction methods do not adapt to individual students. Adaptive learning reverses this practice and attempts to improve the student experience. While adaptive learning is well-established in programming, it is rarely used in cybersecurity education. This paper is one of the first works investigating adaptive learning in cybersecurity training. First, we analyze the performance of 95 students in 12 training sessions to understand the limitations of the current training practice. Less than half of the students (45 out of 95) completed the training without displaying any solution, and only in two sessions, all students completed all phases. Then, we simulate how students would proceed in one of the past training sessions if it would offer more paths of various difficulty. Based on this simulation, we propose a novel tutor model for adaptive training, which considers students' proficiency before and during an ongoing training session. The proficiency is assessed using a pre-training questionnaire and various in-training metrics. Finally, we conduct a case study with 24 students and new training using the proposed tutor model and adaptive training format. The results show that the adaptive training does not overwhelm students as the original static training format. In particular, adaptive training enables students to enter several alternative training phases with lower difficulty than the phases in the original training. The proposed adaptive format is not restricted to particular training used in our case study. Therefore, it can be applied to practicing any cybersecurity topic or even in other related computing fields, such as networking or operating systems. Our study indicates that adaptive learning is a promising approach for improving the student experience in cybersecurity education. We also highlight diverse implications for educational practice that improve students' experience
Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates
Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous disorder with inadequate antibody responses and low levels of immunoglobulins including IgA that is involved in the maintenance of the intestinal homeostasis. In this study, we analyzed the taxonomical and functional metagenome of the fecal microbiota and stool metabolome in a cohort of six CVID patients without gastroenterological symptomatology and their healthy housemates. The fecal microbiome of CVID patients contained higher numbers of bacterial species and altered abundance of thirty-four species. Hungatella hathewayi was frequent in CVID microbiome and absent in controls. Moreover, the CVID metagenome was enriched for low-abundance genes likely encoding nonessential functions, such as bacterial motility and metabolism of aromatic compounds. Metabolomics revealed dysregulation in several metabolic pathways, mostly associated with decreased levels of adenosine in CVID patients. Identified features have been consistently associated with CVID diagnosis across the patients with various immunological characteristics, length of treatment, and age. Taken together, this initial study revealed expansion of bacterial diversity in the host immunodeficient conditions and suggested several bacterial species and metabolites, which have potential to be diagnostic and/or prognostic CVID markers in the future
Engineering the protein dynamics of an ancestral luciferase
Directed evolution commonly relies on point mutations but InDels frequently occur in evolution. Here the authors report a protein-engineering framework based on InDel mutagenesis and fragment transplantation resulting in greater catalysis and longer glow-type bioluminescence of the ancestral luciferase. Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein Anc(HLD-RLuc) which catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of Anc(HLD-RLuc) challenged the scaffold dynamics. Screening for both activities reveals InDel mutations localized in three distinct regions that lead to altered protein dynamics (based on crystallographic B-factors, hydrogen exchange, and molecular dynamics simulations). An anisotropic network model highlights the importance of the conformational flexibility of a loop-helix fragment of Renilla luciferases for ligand binding. Transplantation of this dynamic fragment leads to lower product inhibition and highly stable glow-type bioluminescence. The success of our approach suggests that a strategy comprising (i) constructing a stable and evolvable template, (ii) mapping functional regions by backbone mutagenesis, and (iii) transplantation of dynamic features, can lead to functionally innovative proteins