Programming patterns and development guidelines for Semantic Sensor Grids (SemSorGrid4Env)

The web of Linked Data holds great potential for the creation of semantic applications that can combine self-describing structured data from many sources including sensor networks. Such applications build upon the success of an earlier generation of 'rapidly developed' applications that utilised RESTful APIs. This deliverable details experience, best practice, and design patterns for developing high-level web-based APIs in support of semantic web applications and mashups for sensor grids. Its main contributions are a proposal for combining Linked Data with RESTful application development summarised through a set of design principles; and the application of these design principles to Semantic Sensor Grids through the development of a High-Level API for Observations. These are supported by implementations of the High-Level API for Observations in software, and example semantic mashups that utilise the API

Excess heat might not be entirely from nuclear reactions

Abstract only.During heavy-water electrochemical experiments in the 1980s, Fleischmann and Pons found that more thermal energy came out of their experiments with Pd cathodes than was put in electrically. The excess heat was greater than could be explained by any chemical reactions. Hence, they postulated that the excess energy was due to unexpected nuclear reactions. Now, it is well established experimentally that the amount of excess heat measured in many experiments greatly exceeds what can be attributed to chemistry. For this reason, and also because of numerous reports of nuclear reaction products and energetic radiations, it is widely believed that excess heat is due primarily, and maybe exclusively, to nuclear reactions. Hence, the field is now often called Low Energy Nuclear Reactions. There is an alternative scenario for production of excess heat and the observation of low levels of nuclear reaction products. It is far from new, but has received relatively little attention. Several theorists have postulated the formation of "compact objects" with sizes and energies between those of atoms and nuclei. If such objects do form, they could account for much of the measured excess heat. This paper is a review of the theories of compact objects and their implications

Simulation of the formation of craters in LENR cathode materials

Abstract only.Many electrochemical Low Energy Nuclear Reactions (LENR) experiments have resulted in the observations of micro-craters in the surfaces of the cathode metals (Pd, Au and others). Such craters are not known to form in ordinary electrochemical experiments, that is, without the possibility of LENR. Small craters are of interest for scientific reasons. They indicate the fast and local (high power density) release of energy, much faster than can be captured by calorimeters. Knowing crater formation dynamics might contribute to the understanding of LENR, and also constrain theories about mechanisms and locations of LENR. Cratering might also be practically important, since is erodes the cathode material. No way is known to measure directly the dynamics of crater formation to determine the formation (energy release) time, a key parameter scientifically. Hence, we are using simulations to attempt to learn about the energy production time, the amount of energy liberated, and both the shape and the location of the volume into which energy is released by LENR. There are several commercial software packages, which might be used for the simulations, including ANSYS, ComSol and SolidWorks. We are employing SolidWorks, which permits the initialization of the simulation by designating the cathode material, the release time and total energy, and the geometry of the problem. All of these factors can be varied parametrically in an attempt to produce post-simulation structures similar to those seen in micrographs after LENR experiments. The simulations yield both temporal and spatial distributions of the temperatures that follow from the LENR energy release. We will present the results of simulations of energy releases of 1 nJ to 1 mJ in times from less than 1 nsec to greater than 10 [mu]sec, with a wide range of geometries for the energized volume and its depth below the surface. Estimates of the energy release time and depths are expected to result from the simulation results and their comparisons with experimental micrographs

The poverty of contractarian moral education

In A Theory of Moral Education, Michael Hand claims that a directive moral education that seeks to persuade children that a particular conception of contractarian morality is justified can be undertaken without falling foul of the requirement not to indoctrinate. In this article, we set out a series of challenges to Hand’s argument. First, we argue that Hand’s focus on ‘reasonable disagreement’ regarding the status of a moral conception is a red-herring in this conception. Second, we argue that the endorsement of moral contractarianism and the prohibition on indoctrination pull in different directions: if contractarianism is sound, then teachers or governments should be less worried about indoctrination than Hand suggests. Third, we argue that moral contractarianism is mistaken; teachers should look elsewhere for guidance on the moral norms and principles towards which they should direct their pupils

Distinct conformations, aggregation and cellular internalization of different tau strains

The inter-cellular propagation of tau aggregates in several neurodegenerative diseases involves, in part, recurring cycles of extracellular tau uptake, initiation of endogenous tau aggregation, and extracellular release of at least part of this protein complex. However, human brain tau extracts from diverse tauopathies exhibit variant or “strain” specificity in inducing inter-cellular propagation in both cell and animal models. It is unclear if these distinctive properties are affected by disease-specific differences in aggregated tau conformation and structure. We have used a combined structural and cell biological approach to study if two frontotemporal dementia (FTD)-associated pathologic mutations, V337M and N279K, affect the aggregation, conformation and cellular internalization of the tau four-repeat domain (K18) fragment. In both heparin-induced and native-state aggregation experiments, each FTD variant formed soluble and fibrillar aggregates with remarkable morphological and immunological distinctions from the wild type (WT) aggregates. Exogenously-applied oligomers of the FTD tau-K18 variants (V337M and N279K) were significantly more efficiently taken up by SH-SY5Y neuroblastoma cells than WT tau-K18, suggesting mutation-induced changes in cellular internalization. However, shared internalization mechanisms were observed: endocytosed oligomers were distributed in the cytoplasm and nucleus of SH-SY5Y cells and the neurites and soma of human induced pluripotent stem cell-derived neurons where they co-localized with endogenous tau and the nuclear protein nucleolin. Altogether, evidence of conformational and aggregation differences between WT and disease-mutated tau K18 is demonstrated, which may explain their distinct cellular internalization potencies. These findings may account for critical aspects of the molecular pathogenesis of tauopathies involving WT and mutated tau

In vitro Models for Seizure-Liability Testing Using Induced Pluripotent Stem Cells

The brain is the most complex organ in the body, controlling our highest functions, as well as regulating myriad processes which incorporate the entire physiological system. The effects of prospective therapeutic entities on the brain and central nervous system (CNS) may potentially cause significant injury, hence, CNS toxicity testing forms part of the “core battery” of safety pharmacology studies. Drug-induced seizure is a major reason for compound attrition during drug development. Currently, the rat ex vivo hippocampal slice assay is the standard option for seizure-liability studies, followed by primary rodent cultures. These models can respond to diverse agents and predict seizure outcome, yet controversy over the relevance, efficacy, and cost of these animal-based methods has led to interest in the development of human-derived models. Existing platforms often utilize rodents, and so lack human receptors and other drug targets, which may produce misleading data, with difficulties in inter-species extrapolation. Current electrophysiological approaches are typically used in a low-throughput capacity and network function may be overlooked. Human-derived induced pluripotent stem cells (iPSCs) are a promising avenue for neurotoxicity testing, increasingly utilized in drug screening and disease modeling. Furthermore, the combination of iPSC-derived models with functional techniques such as multi-electrode array (MEA) analysis can provide information on neuronal network function, with increased sensitivity to neurotoxic effects which disrupt different pathways. The use of an in vitro human iPSC-derived neural model for neurotoxicity studies, combined with high-throughput techniques such as MEA recordings, could be a suitable addition to existing pre-clinical seizure-liability testing strategies

Polymeric microspheres as protein transduction reagents

Discovering the function of an unknown protein, particularly one with neither structural nor functional correlates, is a daunting task. Interaction analyses determine binding partners, whereas DNA transfection, either transient or stable, leads to intracellular expression, though not necessarily at physiologically relevant levels. In theory, direct intracellular protein delivery (protein transduction) provides a conceptually simpler alternative, but in practice the approach is problematic. Domains such as HIV TAT protein are valuable, but their effectiveness is protein specific. Similarly, the delivery of intact proteins via endocytic pathways (e.g. using liposomes) is problematic for functional analysis because of the potential for protein degradation in the endosomes/lysosomes. Consequently, recent reports that microspheres can deliver bio-cargoes into cells via a non-endocytic, energy-independent pathway offer an exciting and promising alternative for in vitro delivery of functional protein. In order for such promise to be fully exploited, microspheres are required that (i) are stably linked to proteins, (ii) can deliver those proteins with good efficiency, (iii) release functional protein once inside the cells, and (iv) permit concomitant tracking. Herein, we report the application of microspheres to successfully address all of these criteria simultaneously, for the first time. After cellular uptake, protein release was autocatalyzed by the reducing cytoplasmic environment. Outside of cells, the covalent microsphere-protein linkage was stable for ≥90 h at 37°C. Using conservative methods of estimation, 74.3% ± 5.6% of cells were shown to take up these microspheres after 24 h of incubation, with the whole process of delivery and intracellular protein release occurring within 36 h. Intended for in vitro functional protein research, this approach will enable study of the consequences of protein delivery at physiologically relevant levels, without recourse to nucleic acids, and offers a useful alternative to commercial protein transfection reagents such as Chariot™. We also provide clear immunostaining evidence to resolve residual controversy surrounding FACS-based assessment of microsphere uptake