AhR-activating pesticides increase the bovine ABCG2 efflux activity in MDCKII-bABCG2 cells

In bovine mammary glands, the ABCG2 transporter actively secretes xenobiotics into dairy milk. This can have significant implications when cattle are exposed to pesticide residues in feed. Recent studies indicate that the fungicide prochloraz activates the aryl hydrocarbon receptor (AhR) pathway, increasing bovine ABCG2 (bABCG2) gene expression and efflux activity. This could enhance the accumulation of bABCG2 substrates in dairy milk, impacting pesticide risk assessment. We therefore investigated whether 13 commonly used pesticides in Europe are inducers of AhR and bABCG2 activity. MDCKII cells expressing mammary bABCG2 were incubated with pesticides for up to 72 h. To reflect an in vivo situation, applied pesticide concentrations corresponded to the maximum residue levels (MRLs) permitted in bovine fat or muscle. AhR activation was ascertained through CYP1A mRNA expression and enzyme activity, measured by qPCR and 7-ethoxyresorufin-\u39f-deethylase (EROD) assay, respectively. Pesticide-mediated increase of bABCG2 efflux activity was assessed using the Hoechst 33342 accumulation assay. For all assays, the known AhR-activating pesticide prochloraz served as a positive control, while the non-activating tolclofos-methyl provided the negative control. At 10-fold MRL concentrations, chlorpyrifos-methyl, diflufenican, ioxynil, rimsulfuron, and tebuconazole significantly increased CYP1A1 mRNA levels, CYP1A activity, and bABCG2 efflux activity compared to the vehicle control. In contrast, dimethoate, dimethomorph, glyphosate, iprodione, methiocarb and thiacloprid had no impact on AhR-mediated CYP1A1 mRNA levels, CYP1A activity or bABCG2 efflux. In conclusion, the MDCKII-bABCG2 cell model proved an appropriate tool for identifying AhR- and bABCG2-inducing pesticides. This provides an in vitro approach that could reduce the number of animals required in pesticide approval studies

Design Model For Traceability-Supported Assessment Of Product Carbon Footprint

The established approaches for calculating the Product Carbon Footprint (PCF) based on Life Cycle Assessment (LCA) only allow a cause-related determination of used resources to a limited extent. Even in situations where the direct measurement of resource consumption is recommended, PCF calculation is mainly carried out by means of allocation or estimations in industrial practice. In contrast, the use of traceability data offers promising opportunities for increasing the component specific transparency by linking continuously recorded resource flows and data available in software systems with time stamps and component/order IDs (traceability data). Based on the available component-specific database, companies can identify drivers and hotspots of carbon emissions for individual products and derive targeted measures to reduce these emissions. This paper outlines a concept for a traceability-supported design model to determine the PCF based on the existing framework of LCA. Therefore, a literature review is conducted to identify and analyze existing concepts regarding the determination of PCF as well as requirements for a traceability-supported approach. By conducting an expert survey, these requirements derived from literature are evaluated and prioritized. Finally, the results are used to develop a design model for a traceability supported approach to determine the PCF and to indicate future research needs

Advanced Colloidal Systems for Targeted Chemotherapy

The current project gave a detailed insight of surface modification of different advance colloidal systems along with their in vitro and in vivo targeting capabilities. Three different colloidal systems (nanoparticles, microparticles and liposomes) were evaluated for their efficacies and consistencies in results. The introduction contains an overview for the passive and active targeting of chemotherapeutic agents with different colloidal systems. Different methods of preparation and characterization of these colloidal systems were reviewed. This formed the root level for the use of these formulations in the current project. Furthermore, a brief introduction about aptamers and different examples of targeting molecules was also given to elaborate on aptamers’ specific nature. This provided the basis of surface modification of colloidal formulations with aptamer of interest. Sorafenib tosylate (SFB) was selected as a chemotherapeutic agent because it has low solubility and low bioavailability. Its LogP value is 4.54 with biopharmaceutical classification systems class IV. Systemic toxicity due to non-specific drug delivery is also issues with the use of SFB. Another problem associated with the use of this chemotherapeutic agent is the development of drug resistance after consecutive administrations. Therefore, the current study was designed to improve the efficiency of cancer therapy using sorafenib-loaded colloidal systems coupled with anti-ErbB3-aptamer (Apt). There first part of result and discussion included characterization of SFB-loaded PLGA matrix systems i.e. nanoparticles and microparticles. The encapsulation efficiencies revealed the loading of the drug inside these carrier systems. The physicochemical investigation by Fourier transform infrared spectroscopy, elemental analysis and fluorescence analysis elaborated the success of surface modification of these systems with Apt. Furthermore, morphological analysis by atomic force and scanning electron microscopy supported these results and showed an optimal surface roughness profile for cell surface interactions. Cell culture studies showed a positive impact of the combination of SFB and Apt. The presence of SFB and Apt together showed maximum cytotoxicities compared to other formulations. Dose-dependent toxicities were demonstrated using the cell viability assay. Moreover, time-dependent formulation delivery, to the cytoplasm and subsequently to the nuclear membrane, was observed by CLSM visualization. Higher reactive oxygen species production was observed in the presence of both SFB and Apt as compared to blank formulations. However, the aptamer alone did not significantly induce ROS production. Upon treatment of the cells with different concentration of particles, a significant dose-dependent ROS production was noticed. The metastatic inhibition by the particles, especially those with SFB and Apt was evident from the scratch test. The absence of both SFB and Apt resulted in complete healing of wound within 24 h. Ex vivo hemolysis studies demonstrated the hemocompatibility of the PLGA matrices, thus mimicking in vivo safety of these formulations. The presence of SFB as well Apt did not change the hemolytic potential of formulations to much extent. All the formulations were more hemocampatible as compared to pure drug. Moreover, RBC aggregation test showed no profound change in the morphology of RBCs. In vivo assessment by the blood profiles along with serum biochemistry stamped the safety of the formulation. Nevertheless, heart and liver-specific toxicities were evident in the presence of SFB and Apt but the overall body visceral index was normal. Results and discussion also included characterization of SFB-loaded liposomes. The physicochemical investigation of the liposomes using dynamic light scattering and laser Doppler velocimetry revealed nearly monomodel size range from 121 nm to 155 nm suitable for cellular internalization. However, the presence of SFB and Apt influenced the hydrodynamic diameters and zeta potentials of formulations. Furthermore, morphological characteristics were described by atomic force microscopy and showed optimal sizes and surface roughness profile for cell surface interactions. Synergistic dose-dependent cytotoxicities were demonstrated using SFB and Apt in liposomes in 2D cell culture techniques. The evaluation of toxicity was also visualized in 3D cell cultures and revealed a decrease in 3D culture sizes. This effect was also evident in apoptosis assay showing nuclear condensation as a possible mechanism of cell death. The presence of surface-modified liposomes, inside cells was visualized using CLSM. These investigations showed the presence of liposomes inside the cell, especially near the nuclear region (co-localization coefficient; 0.4-0.7). In order to analyze the in vivo safety as well as the transfection potential of surface modified liposomes the chorioallantoic membrane model (CAM) was used. The presence of these formulations in the mesoderm of the CAM was visualized by CLSM. No evidence of clear toxicity was observed on the development of the embryo. Furthermore, the hemocompatibility studies of liposomes also demonstrated the safety of these formulations when compared to pure drug. Therefore, the combination of chemotherapeutic agent and aptamer together with colloidal drug delivery systems will pave the way to a powerful tool in anticancer therapies. Moreover, the presence of aptamer will also solve the problems of side effects of chemotherapeutic agents by specifically delivering the drug to resistant tumors

Cloud Computing in the Financial Industry – A Road Paved with Security Pitfalls?

In the financial industry, Information Technology (IT) is an essential production factor, but also a major expense post. Because cloud computing promises to deliver IT services more flexibly and cost-efficiently, it potentially constitutes a “perfect match” for the financial sector. However, given the high degree of regulation, concerns regarding security and compliance requirements arise. In this work, we provide a detailed theoretical analysis of potential security problems in the context of cloud computing. This analysis is complemented by the initial results of an ongoing case study concerning the practical relevance of these problems in the financial industry. The analysis confirms that security issues pose notable obstacles for the adoption of cloud computing in practice, but also points to appropriate countermeasures

Epidemiologische Studie zur Entwicklung von MRSA (Methicillin-resistente Staphylococcus aureus) in ökologisch wirtschaftenden Schweinebetrieben

In den letzten Jahren gewinnt das Vorkommen der nutztierassoziierter MRSA (livestock associated MRSA) in Schweinebeständen zunehmend an Bedeutung. In dieser Studie sollte das Vorkommen von MRSA in ökologisch wirtschaftenden Schweinebeständen untersucht werden Dazu wurden 42 ökologisch wirtschaftende Bestände unterschiedlicher Produktionsstufen (Mastbestände, Ferkelerzeuger, geschlossene Systeme) im gesamten Bundesgebiet beprobt. Im Vergleich zu den Ergebnissen des EH-Verbundvorhabens des BMELV zur MRSA-Problematik in konventionell wirtschaftenden Schweinebeständen ist das Vorkommen von MRSA in ökologisch bewirtschafteten Schweinebeständen erheblich geringer. Die Bestimmung der spa-Typen der MRSA-Isolate aus insgesamt 11 MSRA-positiven ökologisch wirtschaftenden Schweinebeständen ergab ein gehäuftes Auftreten der spa-Typen t011 und t034. Diese spa-Typen werden dem Komplex der livestock-associated MRSA zugeordnet und sind auch in konventionell wirtschaftenden Beständen gehäuft nachgewiesen worden. Bei der Ausbreitung von MRSA handelt es sich um ein multifaktorielles Geschehen. Die größte Bedeutung kommt dabei vermutlich dem vergleichsweise geringen Tierverkehr und der bevorzugten Betriebsform des geschlossenen Systems in der ökologischen Landwirtschaft zu. Dies führt voraussichtlich zu einem verminderten Risiko des Eintrags von MRSA. Zudem können sich MRSA, die möglicherweise über Tierzukauf oder Remontierung von Jungsauen in den Bestand gelangt sind, schlechter ausbreiten. Es gilt nun, die Eintragsquellen von MRSA in die ökologische Schweinehaltung in weiterführenden Studien zu untersuchen und durch regelmäßige Untersuchungen von Tieren und Umgebung die Ausbreitung von MRSA weiter einzudämmen

Developing and evaluating a five minute phishing awareness video

Confidence tricksters have always defrauded the unwary. The computer era has merely extended their range and made it possible for them to target anyone in the world who has an email address. Nowadays, they send phishing messages that are specially crafted to deceive. Improving user awareness has the potential to reduce their effectiveness. We have previously developed and empirically-validated phishing awareness programmes. Our programmes are specifically designed to neutralize common phish-related misconceptions and teach people how to detect phishes. Many companies and individuals are already using our programmes, but a persistent niggle has been the amount of time required to complete the awareness programme. This paper reports on how we responded by developing and evaluating a condensed phishing awareness video that delivered phishing awareness more efficiently. Having watched our video, participants in our evaluation were able to detect phishing messages significantly more reliably right after watching the video (compared to before watching the video). This ability was also demonstrated after a retention period of eight weeks after first watching the video