Afocused libraryof furanopyrimidine (350 compounds)was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit 1a was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity inHCT-116 colon cancer cell line. On the basis of docking studieswithEGFRhit 1s, introduction of acrylamideMichael acceptor group led to 8, which inhibited both the wild andmutant EGFRkinase and also showedantiproliferative activity inHCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.

This paper presents an algorithm for content-based forwarding, an essential function in content-based networking. Unlike in traditional address-based unicast or multicast networks, where messages are given explicit destination addresses, the movement of messages through a content-based network

This paper describes a set of interfaces for augmenting fast-forward and rewind on consumer digital video recorders. Our method overlays a series of images sampled from the video over top of the traditional full screen accelerated playback. This sequence creates a trail that provides contextual

We consider combined stimulated Raman adiabatic passage (STIRAP) and fast-forward field (FFF) control of selective vibrational population transfer in a polyatomic molecule. The motivation for using this combination control scheme is twofold: (i) to overcome transfer inefficiency that occurs when

Fast-Forward, abbreviated FF, was the most successful automatic planner in the AIPS-2000 planning systems competition. Like the well known HSP system, FF relies on forward search in the state space, guided by a heuristic that estimates goal distances by ignoring delete lists. It differs from

As cluster services become increasingly complex, awareness of the capabilities of those services are pushed back into the network, and service-aware networking components are now common. Traffic entering and exiting cluster services is likely to be forwarded through a front-end as the performance

The Concept Reader launch was delivered in what we may one day view as a time of great social upheaval. Many widely held values and rights are being challenged by the Conservative-led neoliberal agenda of austerity. In our communities of place, interest and practice we now need to come together, debate and organise. With the launch, Ian Fyfe and Stuart Moir provided us with a platform to think critically and creatively about the current direction of youth work and our ability to influence it. During the seminar a real and troubling sense of discord emerged between the current state of practice and our aspirations for the field. The attendees shared deep concerns about the long term future of democratic Youth Work under an austerity regime that punishes the most vulnerable groups within society and ideologically re-imagines education as an instrumental process towards low wage, insecure employability. ‘If you want to serve the age, betray it ’ Brendan Kennelly (1991, p17). We face a struggle to preserve the democratic traditions and radical origins of Youth Work from marketisation and instrumentalisation which parallel the wider struggle to maintain socially democratic institutions in the country at large. Youth Workers traditionally aim to expose received ideas, media stereotypes and ruling paradigms, and we encourage young people to critically reflect on dominant political narratives. ‘The great enemy of clear language is insincerity ’ George Orwell (1945).

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