Integration, management and communication of heterogeneous design resources with WWW technologies

Recently, advanced information technologies have opened new pos-sibilities for collaborative designs. In this paper, a Web-based collaborative de-sign environment is proposed, where heterogeneous design applications can be integrated with a common interface, managed dynamically for publishing and searching, and communicated with each other for integrated multi-objective de-sign. The CORBA (Common Object Request Broker Architecture) is employed as an implementation tool to enable integration and communication of design application programs; and the XML (eXtensible Markup Language) is used as a common data descriptive language for data exchange between heterogeneous applications and for resource description and recording. This paper also intro-duces the implementation of the system and the encapsulating issues of existing legacy applications. At last, an example of gear design based on the system is il-lustrated to identify the methods and procedure developed by this research

Droplet-based digital antibiotic susceptibility screen reveals single-cell clonal heteroresistance in an isogenic bacterial population

Since antibiotic resistance is a major threat to global health, recent observations that the traditional test of minimum inhibitory concentration (MIC) is not informative enough to guide effective antibiotic treatment are alarming. Bacterial heteroresistance, in which seemingly susceptible isogenic bacterial populations contain resistant sub-populations, underlies much of this challenge. To close this gap, here we developed a droplet-based digital MIC screen that constitutes a practical analytical platform for quantifying the single-cell distribution of phenotypic responses to antibiotics, as well as for measuring inoculum effect with high accuracy. We found that antibiotic efficacy is determined by the amount of antibiotic used per bacterial colony forming unit (CFU), not by the absolute antibiotic concentration, as shown by the treatment of beta-lactamase-carrying Escherichia coli with cefotaxime. We also noted that cells exhibited a pronounced clustering phenotype when exposed to near-inhibitory amounts of cefotaxime. Overall, our method facilitates research into the interplay between heteroresistance and antibiotic efficacy, as well as research into the origin and stimulation of heterogeneity by exposure to antibiotics. Due to the absolute bacteria quantification in this digital assay, our method provides a platform for developing reference MIC assays that are robust against inoculum-density variations

Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment

BACKGROUND: Docetaxel chemotherapy in prostate cancer has a modest impact on survival. To date, efforts to develop combination therapies have not translated into new treatments. We sought to develop a novel therapeutic strategy to tackle chemoresistant prostate cancer by enhancing the efficacy of docetaxel. METHODS: We performed a drug-repurposing screen by using murine-derived prostate cancer cell lines driven by clinically relevant genotypes. Cells were treated with docetaxel alone, or in combination with drugs (n = 857) from repurposing libraries, with cytotoxicity quantified using High Content Imaging Analysis. RESULTS: Mebendazole (an anthelmintic drug that inhibits microtubule assembly) was selected as the lead drug and shown to potently synergise docetaxel-mediated cell killing in vitro and in vivo. Dual targeting of the microtubule structure was associated with increased G2/M mitotic block and enhanced cell death. Strikingly, following combined docetaxel and mebendazole treatment, no cells divided correctly, forming multipolar spindles that resulted in aneuploid daughter cells. Liposomes entrapping docetaxel and mebendazole suppressed in vivo prostate tumour growth and extended progression-free survival. CONCLUSIONS: Docetaxel and mebendazole target distinct aspects of the microtubule dynamics, leading to increased apoptosis and reduced tumour growth. Our data support a new concept of combined mebendazole/docetaxel treatment that warrants further clinical evaluation

EbbRT: a customizable operating system for cloud applications

Efficient use of hardware requires operating system components be customized to the application workload. Our general purpose operating systems are ill-suited for this task. We present Genesis, a new operating system that enables per-application customizations for cloud applications. Genesis achieves this through a novel heterogeneous distributed structure, a partitioned object model, and an event-driven execution environment. This paper describes the design and prototype implementation of Genesis, and evaluates its ability to improve the performance of common cloud applications. The evaluation of the Genesis prototype demonstrates memcached, run within a VM, can outperform memcached run on an unvirtualized Linux. The prototype evaluation also demonstrates an 14% performance improvement of a V8 JavaScript engine benchmark, and a node.js webserver that achieves a 50% reduction in 99th percentile latency compared to it run on Linux

Behavioural simulation of biological neuron systems using VHDL and VHDL-AMS

The investigation of neuron structures is an incredibly difficult and complex task that yields relatively low rewards in terms of information from biological forms (either animals or tissue). The structures and connectivity of even the simplest invertebrates are almost impossible to establish with standard laboratory techniques, and even when this is possible it is generally time consuming, complex and expensive. Recent work has shown how a simplified behavioural approach to modelling neurons can allow “virtual” experiments to be carried out that map the behaviour of a simulated structure onto a hypothetical biological one, with correlation of behaviour rather than underlying connectivity. The problems with such approaches are numerous. The first is the difficulty of simulating realistic aggregates efficiently, the second is making sense of the results and finally, it would be helpful to have an implementation that could be synthesised to hardware for acceleration. In this paper we present a VHDL implementation of Neuron models that allow large aggregates to be simulated. The models are demonstrated using a system level VHDL and VHDL-AMS model of the C. Elegans locomotory system

GART: The Gesture and Activity Recognition Toolkit

Presented at the 12th International Conference on Human-Computer Interaction, Beijing, China, July 2007.The original publication is available at www.springerlink.comThe Gesture and Activity Recognition Toolit (GART) is a user interface toolkit designed to enable the development of gesture-based applications. GART provides an abstraction to machine learning algorithms suitable for modeling and recognizing different types of gestures. The toolkit also provides support for the data collection and the training process. In this paper, we present GART and its machine learning abstractions. Furthermore, we detail the components of the toolkit and present two example gesture recognition applications

RNA catalysis in model protocell vesicles.

We are engaged in a long-term effort to synthesize chemical systems capable of Darwinian evolution, based on the encapsulation of self-replicating nucleic acids in self-replicating membrane vesicles. Here, we address the issue of the compatibility of these two replicating systems. Fatty acids form vesicles that are able to grow and divide, but vesicles composed solely of fatty acids are incompatible with the folding and activity of most ribozymes, because low concentrations of divalent cations (e.g., Mg(2+)) cause fatty acids to precipitate. Furthermore, vesicles that grow and divide must be permeable to the cations and substrates required for internal metabolism. We used a mixture of myristoleic acid and its glycerol monoester to construct vesicles that were Mg(2+)-tolerant and found that Mg(2+) cations can permeate the membrane and equilibrate within a few minutes. In vesicles encapsulating a hammerhead ribozyme, the addition of external Mg(2+) led to the activation and self-cleavage of the ribozyme molecules. Vesicles composed of these amphiphiles grew spontaneously through osmotically driven competition between vesicles, and further modification of the membrane composition allowed growth following mixed micelle addition. Our results show that membranes made from simple amphiphiles can form vesicles that are stable enough to retain encapsulated RNAs in the presence of divalent cations, yet dynamic enough to grow spontaneously and allow the passage of Mg(2+) and mononucleotides without specific macromolecular transporters. This combination of stability and dynamics is critical for building model protocells in the laboratory and may have been important for early cellular evolution

Nano-sized Optical Fluorescence Labels And Uses Thereof

A composition is disclosed which is capable of being used for detection, comprising an encapsulated noble metal nanocluster. Methods for preparing the encapsulated noble metal nanoclusters, and methods of using the encapsulated noble metal nanoclusters are also disclosed. The noble metal nanoclusters are preferably encapsulated by a dendrimer or a peptide. The encapsulated noble metal nanoclusters have a characteristic spectral emission, wherein said spectral emission is varied by controlling the nature of the encapsulating material, such as by controlling the size of the nanocluster and/or the generation of the dendrimer, and wherein said emission is used to provide information about a biological state.Georgia Tech Research Corporatio