Bulge formed cooling channels with a variable lead helix on a hollow body of revolution

A method of constructing a nozzle having cooling channels comprises a shell and a liner which are formed into a body of revolution having an axis of revolution. Helical welds are formed to hold the liner and shell to each other with a channel position being defined between each pair of helical welds. Pressurized fluid which may be a gas or a liquid, is introduced between the weld pairs to outwardly bulge the material of at least one of the liner and shell to define the channels

Fabrication development for high-level nuclear waste containers for the tuff repository; Phase 1 final report

This final report completes Phase 1 of an engineering study of potential manufacturing processes for the fabrication of containers for the long-term storage of nuclear waste. An extensive literature and industry review was conducted to identify and characterize various processes. A technical specification was prepared using the American Society of Mechanical Engineers Boiler & Pressure Vessel Code (ASME BPVC) to develop the requirements. A complex weighting and evaluation system was devised as a preliminary method to assess the processes. The system takes into account the likelihood and severity of each possible failure mechanism in service and the effects of various processes on the microstructural features. It is concluded that an integral, seamless lower unit of the container made by back extrusion has potential performance advantages but is also very high in cost. A welded construction offers lower cost and may be adequate for the application. Recommendations are made for the processes to be further evaluated in the next phase when mock-up trials will be conducted to address key concerns with various processes and materials before selecting a primary manufacturing process. 43 refs., 26 figs., 34 tabs

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Rich-Club Phenomenon in the Interactome of P. falciparum—Artifact or Signature of a Parasitic Life Style?

Recent advances have provided a first experimental protein interaction map of the human malaria parasite P. falciparum, which appears to be remotely related to interactomes of other eukaryotes. Here, we present a comparative topological analysis of this experimentally determined web with a network of conserved interactions between proteins in S. cerevisiae, C. elegans and D. melanogaster that have an ortholog in Plasmodium. Focusing on experimental interactions, we find a significant presence of a “rich-club,” a topological characteristic that features an “oligarchy” of highly connected proteins being intertwined with one another. In complete contrast, the network of interologs and particularly the web of evolutionary-conserved interactions in P. falciparum lack this feature. This observation prompts the question of whether this result points to a topological signature of the parasite's biology, since experimentally obtained interactions widely cover parasite-specific functions. Significantly, hub proteins that appear in such an oligarchy revolve around invasion functions, shaping an island of parasite-specific activities in a sea of evolutionary inherited interactions. This presence of a biologically unprecedented network feature in the human malaria parasite might be an artifact of the quality and the methods to obtain interaction data in this organism. Yet, the observation that rich-club proteins have distinctive and statistically significant functions that revolve around parasite-specific activities point to a topological signature of a parasitic life style