Tracing pathway activities with kinase inhibitors and reverse phase protein arrays

Controlling aberrant protein kinase activity is a promising strategy for a variety of diseases, particularly cancer. Hence, the development of kinase inhibitors is currently a focal point for pharmaceutical research. In this study we utilize a chip-based reverse phase protein array (RPA) platform for profiling of kinase inhibitors in cell-based assays. In combination with the planar wave-guide technology the assay system has an absolute LOD down to the low zeptomole range. A431 cell lysates were analyzed for the activation state of key effectors in the epidermal growth factor (EGF) and insulin signaling pathways to validate this model for compound screening. A microtiter-plate format for growing, treating, and lysing cells was shown to be suitable for this approach, establishing the value of the technology as a screening tool for characterization of large numbers of kinase inhibitors against a wide variety of cellular signaling pathways. Moreover, the reverse array format allows rapid development of site-specific phosphorylation assays, since in contrast to ELISA type systems only a single antigen-specific antibody is required.     

A Multi-Criteria Decision Analysis Technique for Stochastic Task Criticality in Project Management

Inherent in project management is the risk that a project fails to meet planned completion deadlines due to delays experienced in individual tasks. As such, certain critical tasks may be candidates for risk management (e.g., the allocation of additional resources such as labor, materials, and equipment) to prevent delays. A common means to identify such critical tasks is with the critical path method (CPM), which identifies a path of tasks in a project network that, when delayed, result in project delays. This work offers a complementary, stochastic approach to CPM that ranks tasks according to their effect on the project completion time distribution, when the distributions of task completion time are delayed. The new hybrid approach is based on the use of a Monte Carlo simulation and a multi-criteria decision analysis technique. Monte Carlo simulation allows for approximating the cumulative distribution function of the total duration of the project, while the multi-criteria decision analysis technique is used to compare and rank the tasks across percentiles of the resulting project completion time distributions. Doing so allows for different percentile weighting schemes to represent decision maker risk preferences. The suggested approach is applied to two project network examples. The examples illustrate that the proposed approach highlights some tasks as risky, which may not always lie on the critical path as identified by CPM. This is valuable for practicing managers as it allows them to properly consider their risk preferences when determining task criticality based on the distribution of project completion time (e.g., emphasizing median vs. upper tail completion time).     

A Novel Particle/Photon Detector Based on a Superconducting Proximity Array of Nanodots

The current frontiers in the investigation of high-energy particles demand for new detection methods. Higher sensitivity to low-energy deposition, high-energy resolution to identify events and improve the background rejection, and large detector masses have to be developed to detect even an individual particle that weakly interacts with ordinary matter. Here, we will describe the concept and the layout of a novel superconducting proximity array which show dynamic vortex Mott insulator to metal transitions, as an ultra-sensitive compact radiation-particle detector.     

Recommendation of RILEM Technical Committee 250-CSM: Test method for Textile Reinforced Mortar to substrate bond characterization

Textile Reinforced Mortar (TRM), also known as Fabric Reinforced Mortar or Fabric Reinforced Cementitious Matrix, composites are an emerging technology for the external repair and strengthening of existing structures. For most applications, the effectiveness of the TRM reinforcement relies on its bond performance. This recommendation identifies the best practice to characterize the bond behaviour of TRM. A shear bond test method is proposed to determine the peak axial stress (associated with the maximum load that can be transferred from the structural member to the externally bonded TRM reinforcement), the stress–slip relationship and the failure mode that controls the TRM-to-substrate load transfer capacity. Guidelines on specimen manufacturing, experimental setup, test execution, and determination of test results are provided.     

Structural Induction and Coinduction in a Fibrational Setting

We present a categorical logic formulation of induction and coinduction principles for reasoning about inductively and coinductively defined types. Our main results provide sufficient criteria for the validity of such principles: in the presence of comprehension, the induction principle for initial algebras is admissible, and dually, in the presence of quotient types, the coinduction principle for terminal coalgebras is admissible. After giving an alternative formulation of induction in terms of binary relations, we combine both principles and obtain a mixed induction/coinduction principle which allows us to reason about minimal solutionsX≅σ(X) whereXmay occur both positively and negatively in the type constructor σ. We further strengthen these logical principles to deal with contexts and prove that such strengthening is valid when the (abstract) logic we consider is contextually/functionally complete. All the main results follow from a basic result about adjunctions between “categories of algebras” (inserters).     

COSAR: hybrid reasoning for context-aware activity recognition

Human activity recognition is a challenging problem for context-aware systems and applications. Research in this field has mainly adopted techniques based on supervised learning algorithms, but these systems suffer from scalability issues with respect to the number of considered activities and contextual data. In this paper, we propose a solution based on the use of ontologies and ontological reasoning combined with statistical inferencing. Structured symbolic knowledge about the environment surrounding the user allows the recognition system to infer which activities among the candidates identified by statistical methods are more likely to be the actual activity that the user is performing. Ontological reasoning is also integrated with statistical methods to recognize complex activities that cannot be derived by statistical methods alone. The effectiveness of the proposed technique is supported by experiments with a complete implementation of the system using commercially available sensors and an Android-based handheld device as the host for the main activity recognition module.     

Privacy in geo-social networks: proximity notification with untrusted service providers and curious buddies

A major feature of the emerging geo-social networks is the ability to notify a user when any of his friends (also called buddies) happens to be geographically in proximity. This proximity service is usually offered by the network itself or by a third party service provider (SP) using location data acquired from the users. This paper provides a rigorous theoretical and experimental analysis of the existing solutions for the location privacy problem in proximity services. This is a serious problem for users who do not trust the SP to handle their location data and would only like to release their location information in a generalized form to participating buddies. The paper presents two new protocols providing complete privacy with respect to the SP and controllable privacy with respect to the buddies. The analytical and experimental analysis of the protocols takes into account privacy, service precision, and computation and communication costs, showing the superiority of the new protocols compared to those appeared in the literature to date. The proposed protocols have also been tested in a full system implementation of the proximity service.     

A coarse-grain reconfigurable architecture for multimedia applications supporting subword and floating-point calculations

Signal processors exploiting ASIC acceleration suffer from sky-rocketing manufacturing costs and long design cycles. FPGA-based systems provide a programmable alternative for exploiting computation parallelism, but the flexibility they provide is not as high as in processor-oriented architectures: HDL or C-to-HDL flows still require specific expertise and a hardware knowledge background. On the other hand, the large size of the configuration bitstream and the inherent complexity of FPGA devices make their dynamic reconfiguration not a very viable approach. Coarse-grained reconfigurable architectures (CGRAs) are an appealing solution but they pose implementation problems and tend to be application specific. This paper presents a scalable CGRA which eases the implementation of algorithms on field programmable gate array (FPGA) platforms. This design option is based on two levels of programmability: it takes advantage of performance and reliability provided by state-of-the-art FPGA technology, and at the same time it provides the user with flexibility, performance and ease of reconfiguration typical of standard CGRAs. The basic cell template provides advanced features such as sub-word SIMD integer and floating-point computation capabilities, as well as saturating arithmetic. Multiple reconfiguration contexts and partial run-time reconfiguration capabilities are provided, tackling this way the problem of high reconfiguration overhead typical of FPGAs. Selected instances of the proposed architecture have been implemented on an Altera Stratix II EP2S180 FPGA. On this system, we mapped some common DSP, image processing, 3D graphics and audio compression algorithms in order to validate our approach and to demonstrate its effectiveness by benchmarking the benefits achieved.     

nSPARQL: A navigational language for RDF

Navigational features have been largely recognized as fundamental for graph database query languages. This fact has motivated several authors to propose RDF query languages with navigational capabilities. In this paper, we propose the query language nSPARQL that uses nested regular expressions to navigate RDF data. We study some of the fundamental properties of nSPARQL and nested regular expressions concerning expressiveness and complexity of evaluation. Regarding expressiveness, we show that nSPARQL is expressive enough to answer queries considering the semantics of the RDFS vocabulary by directly traversing the input graph. We also show that nesting is necessary in nSPARQL to obtain this last result, and we study the expressiveness of the combination of nested regular expressions and SPARQL operators. Regarding complexity of evaluation, we prove that given an RDF graph G and a nested regular expression E, this problem can be solved in time O(|G||E|).