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Influenza A viruses (IAV) can cause severe global pandemic outbreaks. The currently licensed antiviral drugs are not very effective and prone to viral resistance. Thus, novel effective and broadly active drugs are urgently needed. We have identified the cellular Raf/MEK/ERK signaling cascade as crucial for IAV replication and suitable target for an antiviral intervention. Since this signaling cascade is aberrantly activated in many human cancers, several clinically approved inhibitors of Raf and MEK are now available. Here we explored the anti-IAV action of the licensed B-RafV600E inhibitor Vemurafenib. Treatment of B-RafWT cells with Vemurafenib induced a hyperactivation of the Raf/MEK/ERK cascade rather than inhibiting its activation upon IAV infection. Despite this hyperactivation, which has also been confirmed by others, Vemurafenib still strongly limited IAV-induced activation of other signaling cascades especially of p38 and JNK mitogen-activated protein kinase (MAPK) pathways. Most interestingly, Vemurafenib inhibited virus-induced apoptosis via impaired expression of apoptosis inducing cytokines and led to hampered viral protein translation most likely due to the decreased activation of p38 and JNK MAPK. These multiple actions resulted in a profound and broadly active inhibition of viral replication, up to a titer reduction of three orders of a magnitude. Thus, while Vemurafenib did not act similar to MEK inhibitors, it displays strong antiviral properties via a distinct and multi-target mode of action.

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The 2008 annual meeting of the Signal Transduction Society covered a broad spectrum of topics, with signaling in immune cells as the special focus of the meeting. Many of the immune signaling talks concerned B and T lymphocytes in particular; the role of inflammatory cytokines in cancer progression was also addressed. Neoplastic development was also discussed with regard to aspects of cell cycle control, aging, and transformation. Topics extended to signaling pathways induced by bacteria, viruses, and environmental toxins, as well as those involved in differentiation, morphogenesis, and cell death. This international and interdisciplinary scientific gathering induced lively discussions and close interactions between participants.

Das deutsche DVS-Merkblatt 2811 zur qualitativen und auch quantitativen Überprüfung von Draht- Bondverbindungen in Labor und Praxis (Fertigung) - ,Prüfverfahren für Drahtbondverbindungen' - entstand vor über 20 Jahren als Folge intensiver Diskussionen im Industriearbeitskreis AG A2.4 ,Bonden' des DVS [1]. Dieses DVS-Merkblatt 2811 hob sich bereits bei seiner Veröffentlichung im Jahr 1996 deutlich von internationalen Standards (MIL-Std-883, ASTM International [2, 3] durch schärfe Beurteilungskriterien (z. B. minimal zulässige Pullkräfte) ab, kam dadurch auch über die Landesgrenzen hinweg zur industriellen Anwendung und wurde gar eine Art Vorlage für industriespezifische Qualifikationsmaßnahmen. Nun haben sich aber über die Jahre hinweg nicht nur die zu verarbeitenden Drahtmaterialien (neu: Au-Legierungen, Cu, Ag) verändert, sondern auch die vollautomatisch bondbaren Drahtdurchmesser wurden immer kleiner (< 17,5 mm). Ferner war der Test von Dickdraht- oder Bändchen-Bondverbindungen bisher nicht Bestandteil.

For radar applications, the W-band frequency range (75 - 110 GHz) is a good candidate for high-resolution distance measurement and remote detection of small or hidden objects in distances of 10 cm to >> 20 m. As electromagnetic waves in this frequency range can easily penetrate rough atmosphere like fog, smoke or dust, W-band radars are perfectly suited for automotive, aviation, industrial and security applications. Additional benefit is that atmosphere has an absorption minimum at 94 GHz, so relative small output power is sufficient to achieve long range coverage. By combining and enhancing knowledge from the disciplines of heterogeneous integration technology and compound semiconductor-technology, the Fraunhofer Institutes IAF, IPA and IZM developed a miniaturized and low cost 94 GHz radar module. Result of this approach is a highly miniaturized radar module built using a modular approach. The radar components are mounted on a dedicated RF-NF-hybrid PCB while the signal processing is done on a separate board stacked below. This hybrid RF-module is combined with highly integrated digital processing PCB via micro connectors in a way that the radar system and an adapted conical HDPE-lens fit into an aluminum housing of 42x80x27 mm³ with a weight of only 160 grams for the whole module. The paper will describe the technological basis for such a frequency modulated continuous wave [FMCW] W-band radar module and describe in detail the technological features that enabled the assembly of such a miniaturized but high-performance system. The module yields an evaluated distance measurement accuracy of 5 ppm (5 mm deviation per meter target distance) while its low weight and small dimensions pave the way for a variety of new applications, including mobile operation.

The frequent emergence of new influenza viruses in the human population underlines the urgent need for antiviral therapeutics in addition to the preventative vaccination against the seasonal flu. To circumvent the development of resistance, recent antiviral approaches target cellular proteins needed by the virus for efficient replication. We investigated the contribution of the small GTPase Rac1 to the replication of influenza viruses. Inhibition of Rac1 by NSC23766 resulted in impaired replication of a wide variety of influenza viruses, including a human virus strain of the pandemic from 2009 as well as highly pathogenic avian virus strains. Furthermore, we identified a crucial role of Rac1 for the activity of the viral polymerase complex. The antiviral potential of NSC23766 was confirmed in mouse experiments, identifying Rac1 as a new cellular target for therapeutic treatment of influenza virus infections.

Infections with influenza A viruses (IAV) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. Besides vaccination that represents the best option to protect from IAV infections, only two classes of anti-influenza drugs, inhibitors of the M2 ion channel and the neuraminidase, often causing resistant IAV variants have been approved. That is why the need for effective and amply available antivirals against IAV is of high priority. Here we introduce LADANIA067 from the leaves of the wild black currant (Ribes nigrum folium) as a potent compound against IAV infections in vitro and in vivo. LADANIA067 treatment resulted in a reduction of progeny virus titers in cell cultures infected with prototype avian and human influenza virus strains of different subtypes. At the effective dose of 100 µg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation. Further, viruses showed no tendency to develop resistance to LADANIA067 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of LADANIA067 appears to be mainly due to interference with virus internalisation. In the mouse infection model LADANIA067 treatment reduces progeny virus titers in the lung upon intranasal application. In conclusion, an extract from the leaves of the wild black currant might be a promising source for the development of new antiviral compounds to fight IAV infections.

Abundant evidence over past decades shows that foods with added plant sterols and plant stanols lower serum LDL cholesterol concentrations. However, despite the overwhelming data, numerous scientific questions still remain. The objective of this paper is to summarize the considerations of 60 academic and industrial experts who participated in the scientific meeting in Maastricht, the Netherlands, on issues related to the health effects of plant sterols and plant stanols. The meeting participants discussed issues including efficacy profiling, heterogeneity in responsiveness, effects beyond LDL-C lowering, and food formulation aspects of plant sterol and stanol consumption. Furthermore, aspects related to the potential atherogenicity of elevated circulatory plant sterol concentrations were discussed. Until the potential atherogenicity of plant sterols is resolved, based on the results >200 clinical trials, the risk to benefit of plant sterol use is favorable. Evidence on these topics in plant sterol and plant stanol research was presented and used to reach consensus where possible. It was concluded that endpoint studies looking at plant sterol and plant stanol efficacy are needed, however, there was no clear opinion on the best marker and best design for such a study. Based on the current scientific evidence, plant sterols and plant stanols are recommended for use as dietary options to lower serum cholesterol. © 2012.