Fibre composites, and especially aligned discontinuous composites (ADCs), offer enormous versatility in composition, microstructure, and performance, but are difficult to optimise, due to their inherent variability and myriad permutations of microstructural design variables. This work combines an accurate yet efficient virtual testing framework (VTF) with a data-driven intelligent Bayesian optimisation routine, to maximise the mechanical performance of ADCs for a number of single- and multi-objective design cases. The use of a surrogate model helps to minimise the number of optimisation iterations, and provides a more accurate insight into the expected performance of materials which feature significant variability. Results from the single-objective optimisation study show that a wide range of structural properties can be achieved using ADCs, with a maximum stiffness of 505 GPa, maximum ultimate strain of 3.94%, or a maximum ultimate strength of 1.92 GPa all possible. A moderate trade-off in performance can be achieved when considering multi-objective optimisation design cases, such as an optimal ultimate strength & ultimate strain combination of 982 MPa and 3.27%, or an optimal combination of 720 MPa yield strength & 1.91% pseudo-ductile strain.

Aligned hybrid-fibre discontinuous composites offer the ability to tailor their mechanical response through careful microstructural design. However, with tailorability comes microstructural complexity, which in turn leads to many sources of variability and defects. A virtual testing framework was further extended to investigate the influence of variability and defects on the mechanical performance of various aligned discontinuous composite material systems. This approach identified the most critical sources of variability as (i) fibre strength, (ii) the distance between fibre ends, or (iii) the level of fibre-type intermingling, depending on the material system. Fibre vacancy defects were shown to have the most significant influence on the strength and ductility of aligned discontinuous composites, although this sensitivity can be reduced through hybridisation of the fibre types.

Aligned discontinuous composites offer a tailorable structural response, as their mechanical behaviour can be tailored by adjusting their microstructure. However, the stochastic nature of their microstructure, and the myriad permutations of different constituent properties makes optimisation of these materials difficult. In this work, an accurate yet efficient virtual testing framework is combined with an intelligent Bayesian optimisation routine to maximise the initial stiffness, ultimate strain, and ultimate strength of aligned discontinuous composites.

Composite materials often feature defects, particularly for composites which feature a complex microstructure, such as aligned discontinuous composites. This study uses an accurate but efficient virtual testing framework, which was used to predict the influence of defects on the structural performance of both hybrid and nonhybrid aligned discontinuous composites. Fibre vacancy defects were found to cause the strongest reduction in material properties, while hybridisation was found to be an effective means to reduce the influence of defects on the structural response.

Pseudo-ductility presents a potential means for preventing catastrophic failure in composite materials; large deformations will prevent brittle fracture and provide warning before final failure. This work explores how the pseudo-ductility and strength of aligned hybrid discontinuous composites can be controlled by manipulating the arrangement of different fibre types. Aligned carbon/glass hybrid specimens with different fibre arrangements are manufactured and tested using a modification to the High Performance Discontinuous Fibre (HiPerDiF) method. Experimental results are complemented by an improved virtual testing framework, which accurately captures the fracture behaviour of a range of hybrid discontinuous composite microstructures. With a randomly intermingled fibre arrangement as a baseline, a 27% increase in strength and a 44% increase in pseudo-ductility can be achieved when low elongation fibres are completely isolated from one-another. Results demonstrate that the HiPerDiF method is the current state-of-the-art for maximising the degree of intermingling and hence the pseudo-ductility of hybrid composites.

This paper describes different aspects of an open competition to evaluate multicultural name matching software, including the contest design, development of the test data, different phases of the competition, behavior of the participating teams, results of the competition, and lessons learned throughout. The competition, known as The MITRE Challenge (TM), was informally announced at LREC 2010 and was recently concluded. Contest participants used the competition website (http://mitrechallenge.mitre.org) to download the competition data set and guidelines, upload results, and to view accuracy metrics for each result set submitted. Participants were allowed to submit unlimited result sets, with their top-scoring set determining their overall ranking. The competition website featured a leader board that displayed the top score for each participant, ranked according to the principal contest metric - mean average precision (MAP). MAP and other metrics were calculated in near-real time on a remote server, based on ground truth developed for the competition data set. Additional measures were taken to guard against gaming the competition metric or overfilling to the competition data set.

This paper describes the development and evaluation of enhancements to the specialized information retrieval capabilities of a multimodal reporting system. The system enables collection and dissemination of information through a distributed data architecture by allowing users to input free text documents, which are indexed for subsequent search and retrieval by other users. This unstructured data entry method is essential for users of this system, but it requires an intelligent support system for processing queries against the data. The system, known as TIGR ( Tactical Ground Reporting), allows keyword searching and geospatial filtering of results, but lacked the ability to efficiently index and search person names and perform approximate name matching. To improve TIGR's ability to provide accurate, comprehensive results for queries on person names we iteratively updated existing entity extraction and name matching technologies to better align with the TIGR use case. We evaluated each version of the entity extraction and name matching components to find the optimal configuration for the TIGR context, and combined those pieces into a named entity extraction, indexing, and search module that integrates with the current TIGR system. By comparing system-level evaluations of the original and updated TIGR search processes, we show that our enhancements to personal name search significantly improved the performance of the overall information retrieval capabilities of the TIGR system.

The neuritic plaque is a hallmark pathology of Alzheimer's disease (AD), which contains a core composed of Aβ peptide in a stacked β-pleated sheet conformation (“Aβ-amyloid”) bound by activated microglia. Amyloid cores are associated with dystrophic neurites, while non-amyloid brain Aβ deposits have little adverse effect on surrounding neuropil. As prevalence of dystrophic neurites in AD brain correlates with severity of dementia, preventing the appearance of Aβ in its amyloid conformation is a potential therapeutic strategy. Most efforts to model amyloid fibril formation in vitro initiate spontaneous fibril formation by stirring Aβ peptide under highly controlled conditions. However, the ultrastructural relationship between microglia and amyloid fibrils in AD brain suggests that microglia play an active role in the “refolding” of Aβ into amyloid. We investigated this hypothesis by adding freshly solubilized Aβ to plate-bound rat microglia, primary human monocytes and macrophages, differentiated THP-1 cells, and the IC21 mouse peritoneal macrophage line. All cell types were able to refold Aβ peptide into an amyloid conformation as demonstrated by thioflavin-S staining. This effect is specific to cells of monocytoid lineage, including macrophage-differentiated embryonic stem cells, and did not occur in neurons, undifferentiated embryonic stem cells, or H4 cells. In the absence of cells, extensive Aβ precipitates form on the tissue culture plastic (measured using the Aβ-specific antibody 4G8) but these precipitates are nearly devoid of thioflavin-S fluorescence. The amyloidogenic factor does not appear to be soluble as Aβ incubation in microglia-conditioned media does not recapitulate the effect. Transmission electron microscopy of cultures showed clusters of electron-dense fibrils in cytoplasmic channels that often terminated in clathrin-coated heads, a similar pattern to that observed in AD brain and transgenic models. These data support the hypothesis that neuritic plaque formation is an active microglia-mediated process.

Microglia are thought to play an active role in the formation of neuritic plaques in Alzheimer's disease (AD). We have previously demonstrated that microglia and other cells of monocytoid lineage rapidly convert amorphous Aβ deposits into amyloid (assessed by thioflavin-S fluorescence and electron microscopy) using an in-vitro model. This study aimed to further characterize our in-vitro model of microglia-facilitated amyloidogenesis (MFA) to determine the factors regulating its activity. We therefore profiled several agents including cytokines, dexamethasone and HMG-CoA reductase inhibitors (statins). The Th2-promoting cytokines TGFβ and IL-4 both block MFA with low nanomolar potency. This effect is unlikely to be due to direct interaction with Aβ, which is present at 10 μM. The synthetic glucocorticoid receptor agonist dexamethasone also potently blocks MFA but, in contrast to TGFβ, also inhibits Aβ internalization and clearance by microglia (monitored by cell-associated Aβ immunostaining). The effect of dexamethasone on microglial interaction with Aβ is similar to the cytoskeleton-disrupting agent cytochalasin D, which also blocks both MFA and uptake/degradation of Aβ. The profile of these mechanisms in vitro may have relevance in vivo as: 1) overexpression of TGFβ in the brains of hAPP Aβ-depositing transgenic mice greatly decreases formation of parenchymal thioflavin-positive Aβ deposits, consistent with blockade of MFA in vitro; and 2) central administration of dexamethasone is reported to increase levels of brain Aβ by decreasing its clearance, consistent with the blocked clearance of Aβ by dexamethasone observed in cultured microglia. Several statins were also found to inhibit MFA. This inhibition was reversed by mevalonate, indicating involvement of the cholesterol metabolic pathway in regulation of MFA. Recent literature has indicated that chronic statin treatment may suppress the expression of key immune signaling molecules on microglia in AD brain, suggesting central immunomodulatory effects of statins. These data indicate that multiple mechanisms may contribute to MFA. Modulation of these mechanisms may prevent a microglial phenotype that leads to neuritic plaque formation.

Four human B cell lines established by Epstein-Barr viral transformation of B cells from a patient with a clinical diagnosis of Alzheimer's disease (AD) were found to secrete antibodies that react with plaques and cerebrovascular blood vessels in AD brain in a staining profile characteristic of beta-amyloid protein (beta-AP) in AD brain. Two of these antibodies were shown to be reactive with a rare plaque in a normal brain. In these studies, immunofluorescence and avidin-biotin complex immunoperoxidase methodology were used to determine antibody reaction, and thioflavine S was used to double label amyloid and neurofibrillary tangles. The four antibodies also reacted with neurons in normal and AD brain. Absorption studies, dot immunoblots, and enzyme-linked immunosorbent assays with beta-amyloid peptides 1-28 (beta-A1-28) and 1-40 (beta-A1-40) indicate the major determinant of the reactive epitope is located in the region of amino acids 1-28 of beta-AP. However, inhibition studies demonstrate a significant contribution to the antigenic determinant by the 29-40 region of the beta-A1-40. These antibodies represent the first human autoantibodies against beta-AP. The pathological significance of these autoantibodies is discussed.