The 'Sphere': A Dedicated Bifurcation Aneurysm Flow-Diverter Device.

We present flow-based results from the early stage design cycle, based on computational modeling, of a prototype flow-diverter device, known as the 'Sphere', intended to treat bifurcation aneurysms of the cerebral vasculature. The device is available in a range of diameters and geometries and is constructed from a single loop of NITINOL(®) wire. The 'Sphere' reduces aneurysm inflow by means of a high-density, patterned, elliptical surface that partially occludes the aneurysm neck. The device is secured in the healthy parent vessel by two armatures in the shape of open loops, resulting in negligible disruption of parent or daughter vessel flow. The device is virtually deployed in six anatomically accurate bifurcation aneurysms: three located at the Basilar tip and three located at the terminus bifurcation of the Internal Carotid artery (at the meeting of the middle cerebral and anterior cerebral arteries). Both steady state and transient flow simulations reveal that the device presents with a range of aneurysm inflow reductions, with mean flow reductions falling in the range of 30.6-71.8% across the different geometries. A significant difference is noted between steady state and transient simulations in one geometry, where a zone of flow recirculation is not captured in the steady state simulation. Across all six aneurysms, the device reduces the WSS magnitude within the aneurysm sac, resulting in a hemodynamic environment closer to that of a healthy vessel. We conclude from extensive CFD analysis that the 'Sphere' device offers very significant levels of flow reduction in a number of anatomically accurate aneurysm sizes and locations, with many advantages compared to current clinical cylindrical flow-diverter designs. Analysis of the device's mechanical properties and deployability will follow in future publications

Cheetah Acinonyx jubatus behaviour and resource use in response to other African large carnivores

Competition occurs between species for shared resources. Subordinate species employ resource selection to shift their resource use away from that of dominant species in order to avoid the negative consequences of competition. Only in Africa is the post-Pleistocene large carnivore guild intact, consisting of lions Panthera leo, spotted hyaenas Crocuta crocuta, leopards Panthera pardus, cheetahs Acinonyx jubatus, and African wild dogs Lycaon pictus. Therefore, only in Africa can we explore how large carnivores co-exist with one another in a diverse community. Cheetahs are a subordinate member of the large carnivore guild due to their small stature and solitary nature. However, we still do not fully understand how competition shapes cheetah behaviour and resource use. I used cheetahs as a model subordinate predator to determine the behavioural responses and resource selection of cheetah in response to assumed competition from other large carnivores. I experimentally explored the behavioural response of cheetah to large carnivore scent sources (scats) and their presence at cheetah scent-marking sites to test for avoidance of such cues. Moreover, using unplanned experiments based on the resource use of cheetahs in the absence and then presence of lions (assessing space and time use by cheetah) and African wild dogs (assessing prey use by both species), I evaluated resource selection by cheetahs as a way to reduce competition with these large carnivores. In addition, I measured spatial and temporal partitioning between cheetahs and all four large carnivores at camera trap sites. Finally, I assessed whether cheetahs responded to competitors using a long term proactive response or a short term reactive response. I found that all four of the other large carnivores in the guild shaped cheetahs resource use, however, all did so on different axes in accordance with the niche complementarity hypothesis. Lions and spotted hyenas were avoided through time, African wild dogs through space and prey use, and lions and leopards on the spatiotemporal axis. Moreover, I show that cheetahs utilize a reactive response to competition that allows them to avoid risk while still obtaining necessary resources

Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning

Offside goals and induced breaches of contract

An analysis of Global Resources Group Ltd v Mackay which explores the possibility of building links between the offside goals rule and nominate delict of inducing breach of contract

Cheetah Acinonyx jubatus behaviour and resource use in response to other African large carnivores

Competition occurs between species for shared resources. Subordinate species employ resource selection to shift their resource use away from that of dominant species in order to avoid the negative consequences of competition. Only in Africa is the post-Pleistocene large carnivore guild intact, consisting of lions Panthera leo, spotted hyaenas Crocuta crocuta, leopards Panthera pardus, cheetahs Acinonyx jubatus, and African wild dogs Lycaon pictus. Therefore, only in Africa can we explore how large carnivores co-exist with one another in a diverse community. Cheetahs are a subordinate member of the large carnivore guild due to their small stature and solitary nature. However, we still do not fully understand how competition shapes cheetah behaviour and resource use. I used cheetahs as a model subordinate predator to determine the behavioural responses and resource selection of cheetah in response to assumed competition from other large carnivores. I experimentally explored the behavioural response of cheetah to large carnivore scent sources (scats) and their presence at cheetah scent-marking sites to test for avoidance of such cues. Moreover, using unplanned experiments based on the resource use of cheetahs in the absence and then presence of lions (assessing space and time use by cheetah) and African wild dogs (assessing prey use by both species), I evaluated resource selection by cheetahs as a way to reduce competition with these large carnivores. In addition, I measured spatial and temporal partitioning between cheetahs and all four large carnivores at camera trap sites. Finally, I assessed whether cheetahs responded to competitors using a long term proactive response or a short term reactive response. I found that all four of the other large carnivores in the guild shaped cheetahs resource use, however, all did so on different axes in accordance with the niche complementarity hypothesis. Lions and spotted hyenas were avoided through time, African wild dogs through space and prey use, and lions and leopards on the spatiotemporal axis. Moreover, I show that cheetahs utilize a reactive response to competition that allows them to avoid risk while still obtaining necessary resources

An RNAi-mediated genetic screen identifies genes that promote tumour progression in a living epithelium

The complex process by which cancer cells invade local tissue and metastasise is responsible for approximately 90% of cancer related deaths. The cell biological events that underlie this transition to malignancy are driven by invariable alterations within the genome, however relatively little is known about the genetic determinants involved. If identified, novel genes which perturb the rate of tumour progression could become potential targets for future therapeutic intervention. Using a novel in vivo system, it is possible to characterise the behaviour of transformed cells during the early stages of tumour development and follow these cells in real time, thus improving our understanding of the critical events that initiate cell proliferation, tumour cell invasion and metastasis. Using Drosophila as a model organism it is possible to generate neoplastic tumours within the dorsal thorax whereby clones of transformed cells are homozygous mutant for a specific tumour suppressor gene. By specifically labelling these transformed cells with GFP, their behaviour can be observed in high temporal and spatial resolution within the living epithelium. RNAi technology can also be employed to simultaneously knock-down expression of an additional gene specifically within the mutant tissue. This forms the basis of a large-scale screen for novel genes that may promote tumour progression in this epithelium. The screen is now almost complete and so far we have screened through almost 500 genes, the majority of which have previously been implicated in cancer but remain uncharacterised. We have observed a wide range of phenotypes, with genes affecting cell proliferation, invasion, cell shape, actin organisation, junction integrity and epithelial multilayering. By setting ‘thresholds’ for particular phenotypes ‘hits’ have been identified which drastically enhance tumour progression, and these genes are in the process of being fully characterised to further our understanding of their role in tumour progression

An RNAi-mediated genetic screen identifies genes that promote tumour progression in a living epithelium

The complex process by which cancer cells invade local tissue and metastasise is responsible for approximately 90% of cancer related deaths. The cell biological events that underlie this transition to malignancy are driven by invariable alterations within the genome, however relatively little is known about the genetic determinants involved. If identified, novel genes which perturb the rate of tumour progression could become potential targets for future therapeutic intervention. Using a novel in vivo system, it is possible to characterise the behaviour of transformed cells during the early stages of tumour development and follow these cells in real time, thus improving our understanding of the critical events that initiate cell proliferation, tumour cell invasion and metastasis. Using Drosophila as a model organism it is possible to generate neoplastic tumours within the dorsal thorax whereby clones of transformed cells are homozygous mutant for a specific tumour suppressor gene. By specifically labelling these transformed cells with GFP, their behaviour can be observed in high temporal and spatial resolution within the living epithelium. RNAi technology can also be employed to simultaneously knock-down expression of an additional gene specifically within the mutant tissue. This forms the basis of a large-scale screen for novel genes that may promote tumour progression in this epithelium. The screen is now almost complete and so far we have screened through almost 500 genes, the majority of which have previously been implicated in cancer but remain uncharacterised. We have observed a wide range of phenotypes, with genes affecting cell proliferation, invasion, cell shape, actin organisation, junction integrity and epithelial multilayering. By setting ‘thresholds’ for particular phenotypes ‘hits’ have been identified which drastically enhance tumour progression, and these genes are in the process of being fully characterised to further our understanding of their role in tumour progression

Improving Responsiveness of Time-Sensitive Applications by Exploiting Dynamic Task Dependencies

In this paper, a mechanism is presented for reducing priority inversion in multi-programmed computing systems. Contrarily to well-known approaches from the literature, this paper tackles cases where the dependency relationships among tasks cannot be known in advance to the operating system (OS). The presented mechanism allows tasks to explicitly declare said relationships, enabling the OS scheduler to take advantage of such information and trigger priority inheritance, resulting in reduced priority inversion. We present the prototype implementation of the concept within the Linux kernel, in the form of modifications to the standard POSIX condition variables code, along with an extensive evaluation including a quantitative assessment of the benefits for applications making use of the technique, as well as comprehensive overhead measurements. Also, we present an associated technique for theoretical schedulability analysis of a system using the new mechanism, which is useful to determine whether all tasks can meet their deadlines or not, in the specific scenario of tasks interacting only through remote procedure calls, and under partitioned scheduling

Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex

<p>Abstract</p> <p>Background</p> <p>The arachnoid granulations (AGs) are herniations of the arachnoid membrane into the dural venous sinuses on the surface of the brain. Previous morphological studies of AGs have been limited in scope and only one has mentioned surface area measurements. The purpose of this study was to investigate the topographic distribution of AGs on the superior surface of the cerebral cortex.</p> <p>Methods</p> <p><it>En face </it>images were taken of the superior surface of 35 formalin-fixed human brains. AGs were manually identified using Adobe Photoshop, with a pixel location containing an AG defined as 'positive'. A set of 25 standard fiducial points was marked on each hemisphere for a total of 50 points on each image. The points were connected on each hemisphere to create a segmented image. A standard template was created for each hemisphere by calculating the average position of the 25 fiducial points from all brains. Each segmented image was mapped to the standard template using a linear transformation. A topographic distribution map was produced by calculating the proportion of AG positive images at each pixel in the standard template. The AG surface area was calculated for each hemisphere and for the total brain superior surface. To adjust for different brain sizes, the proportional involvement of AGs was calculated by dividing the AG area by the total area.</p> <p>Results</p> <p>The total brain average surface area of AGs was 78.53 ± 13.13 mm²(n = 35) and average AG proportional involvement was 57.71 × 10^-4± 7.65 × 10^-4. Regression analysis confirmed the reproducibility of AG identification between independent researchers with r²= 0.97. The surface AGs were localized in the parasagittal planes that coincide with the region of the lateral lacunae.</p> <p>Conclusion</p> <p>The data obtained on the spatial distribution and <it>en face </it>surface area of AGs will be used in an <it>in vitro </it>model of CSF outflow. With an increase in the number of samples, this analysis technique can be used to study the relationship between AG surface area and variables such as age, race and gender.</p

CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity

Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila, reduces the junctional localization of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity