A Scalable Middleware Solution for Advanced Wide Area Web Services

To alleviate scalability problems in the Web, many researchers concentrate on how to incorporate advanced caching and replication techniques. Many solutions incorporate object-based techniques. In particular, Web resources are considered as distributed objects offering a well-defined interface. We argue that most proposals ignore two important aspects. First, there is little discussion on what kind of coherence should be provided. Proposing specific caching or replication solutions makes sense only if we know what coherence model they should implement. Second, most proposals treat all Web resources alike. Such a one-size-fits-all approach will never work in a wide-area system. We propose a solution in which Web resources are encapsulated in physically distributed shared objects. Each object should encapsulate not only state and operations, but also the policy by which its state is distributed, cached, replicated, migrated, etc

Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity

Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer's disease with toxicities mimicked by synthetic Aβ1-42. However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ1-42 after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer's disease

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

Human performance and strategies while solving an aircraft routing and sequencing problem: an experimental approach

As airport resources are stretched to meet increasing demand for services, effective use of ground infrastructure is increasingly critical for ensuring operational efficiency. Work in operations research has produced algorithms providing airport tower controllers with guidance on optimal timings and sequences for flight arrivals, departures, and ground movement. While such decision support systems have the potential to improve operational efficiency, they may also affect users’ mental workload, situation awareness, and task performance. This work sought to identify performance outcomes and strategies employed by human decision makers during an experimental airport ground movement control task with the goal of identifying opportunities for enhancing user-centered tower control decision support systems. To address this challenge, thirty novice participants solved a set of vehicle routing problems presented in the format of a game representing the airport ground movement task practiced by runway controllers. The games varied across two independent variables, network map layout (representing task complexity) and gameplay objective (representing task flexibility), and verbal protocol, visual protocol, task performance, workload, and task duration were collected as dependent variables. A logistic regression analysis revealed that gameplay objective and task duration significantly affected the likelihood of a participant identifying the optimal solution to a game, with the likelihood of an optimal solution increasing with longer task duration and in the less flexible objective condition. In addition, workload appeared unaffected by either independent variable, but verbal protocols and visual observations indicated that high-performing participants demonstrated a greater degree of planning and situation awareness. Through identifying human behavior during optimization problem solving, the work of tower control can be better understood, which, in turn, provides insights for developing decision support systems for ground movement management

Mitochondrial dynamics regulate cell morphology in the developing cochlea

In multicellular tissues, the size and shape of cells are intricately linked with their physiological functions. In the vertebrate auditory organ, the neurosensory epithelium develops as a mosaic of sensory hair cells (HCs), and their glial-like supporting cells, which have distinct morphologies and functional properties at different frequency positions along its tonotopic long axis. In the chick cochlea, the basilar papilla (BP), proximal (high-frequency) HCs, are larger than their distal (low-frequency) counterparts, a morphological feature essential for sound perception. Mitochondrial dynamics, which constitute the equilibrium between fusion and fission, regulate differentiation and functional refinement across a variety of cell types. We investigate this as a potential mechanism for regulating the shape of developing HCs. Using live imaging in intact BP explants, we identify distinct remodelling of mitochondrial networks in proximal compared with distal HCs. Manipulating mitochondrial dynamics in developing HCs alters their normal morphology along the proximal-distal (tonotopic) axis. Inhibition of the mitochondrial fusion machinery decreased proximal HC surface area, whereas promotion of fusion increased the distal HC surface area. We identify mitochondrial dynamics as a key regulator of HC morphology in developing inner ear epithelia

Response of Siliceous Marine Organisms to the Permian-Triassic Climate Crisis Based on New Findings From Central Spitsbergen, Svalbard

Siliceous marine ecosystems play a critical role in shaping the Earth's climate system by influencing rates of organic carbon burial and marine authigenic clay formation (i.e., reverse weathering). The ecological demise of silicifying organisms associated with the Permian-Triassic mass extinction is postulated to have elevated marine authigenic clay formation rates, resulting in a prolonged greenhouse climate during the Early Triassic. Yet, our understanding of the response of siliceous marine organisms during this critical interval is poor. Whilst radiolarians experienced the strongest diversity loss in their evolutionary history and perhaps also the greatest population decline of silica-secreting organisms during this event, only a small number of Griesbachian (post-extinction) localities that record siliceous organisms are known. Here, we report newly discovered latest Changhsingian to early Griesbachian (Clarkina meishanensis - Hindeodus parvus Zone) radiolarians and siliceous sponge spicules from Svalbard. This fauna documents the survival of a low-diversity radiolarian assemblage alongside stem-group hexactinellid sponges making this the first described account of post-extinction silica-secreting organisms from the Permian/Triassic boundary in a shallow marine shelf environment and a mid-northern paleolatitudinal setting. Our findings indicate that latitudinal diversity gradients for silica-secreting organisms following the mass extinction were significantly altered, and that silica productivity was restricted to high latitude and deep water thermal refugia. This result has potential to further shape our understanding of changes in marine dissolved silica levels and in turn rates of reverse weathering, with implications for our understanding of carbon cycle dynamics during this interval

Ghosts of Yellowstone: Multi-Decadal Histories of Wildlife Populations Captured by Bones on a Modern Landscape

Natural accumulations of skeletal material (death assemblages) have the potential to provide historical data on species diversity and population structure for regions lacking decades of wildlife monitoring, thereby contributing valuable baseline data for conservation and management strategies. Previous studies of the ecological and temporal resolutions of death assemblages from terrestrial large-mammal communities, however, have largely focused on broad patterns of community composition in tropical settings. Here, I expand the environmental sampling of large-mammal death assemblages into a temperate biome and explore more demanding assessments of ecological fidelity by testing their capacity to record past population fluctuations of individual species in the well-studied ungulate community of Yellowstone National Park (Yellowstone). Despite dramatic ecological changes following the 1988 wildfires and 1995 wolf re-introduction, the Yellowstone death assemblage is highly faithful to the living community in species richness and community structure. These results agree with studies of tropical death assemblages and establish the broad capability of vertebrate remains to provide high-quality ecological data from disparate ecosystems and biomes. Importantly, the Yellowstone death assemblage also correctly identifies species that changed significantly in abundance over the last 20 to ∼80 years and the directions of those shifts (including local invasions and extinctions). The relative frequency of fresh versus weathered bones for individual species is also consistent with documented trends in living population sizes. Radiocarbon dating verifies the historical source of bones from Equus caballus (horse): a functionally extinct species. Bone surveys are a broadly valuable tool for obtaining population trends and baseline shifts over decadal-to-centennial timescales

The treatment-related experiences of parents, children and young people with regular prescribed medication

Background Taking regular medication has been shown to have an impact on the daily lives of patients and their families. Objective To explore the medication-related experiences of patients and their families when a child or young person is prescribed regular medication. Setting A specialist U.K. paediatric hospital. Method Semi-structured face-to-face interviews of 24 parents/carers, children or young people, who had been taking two or more medications for 6 weeks or longer. The themes explored included the medication regimen, formulation, supplies, social aspects and adverse effects. The data was analysed using NVIVO version 11. Main outcome measure The experiences of patients, and their parents/carers, when a child/young person takes regular medication. Results Participants described a range of experiences associated with taking regular medication. Medication-related challenges were experienced around the timing of administration which was managed over 24 h rather than waking hours. Updating medication doses for administration at school was often delayed. Unintended nonadherence was cited as the biggest challenge with a range of strategies employed to manage this. The internet was commonly used as a source of additional information accessed for reassurance and adverse effects but there were varying experiences of using patient forums/help groups. Other challenges included the adequacy of information, travelling with medication, formulation issues, arranging supplies and adverse effects. Conclusion Patients and parents experience many challenges with children’s medication. Individualised treatment options should be considered. Further research is required to determine how these experiences may be managed including the role of paediatric medication review

Effects of spines and thorns on Australian arid zone herbivores of different body masses

We investigated the effects of thorns and spines on the feeding of 5 herbivore species in arid Australia. The herbivores were the rabbit ( Oryctolagus cuniculus ), euro kangaroo ( Macropus robustus ), red kangaroo ( Macropus rufus ), sheep ( Ovis aries ), and cattle ( Bos taurus ). Five woody plants without spines or thorns and 6 woody plants with thorns were included in the study. The spines and thorns were not found to affect the herbivores' rates of feeding (items ingested/min), but they did reduce the herbivores' rates of biomass ingestion (g-dry/item). The reduction in biomass ingested occurred in two ways: at a given diameter, twigs with spines and thorns had less mass than undefended plants, and the herbivores consumed twigs with smaller diameters on plants with spines and thorns. The relative importance of the two ways that twigs with spines and thorns provided less biomass varied with herbivore body mass. Reduced twig mass was more important for small herbivores, while large herbivores selected smaller diameters. The effectiveness of spines and thorns as anti-herbivore defenses did not vary with the evolutionary history of the herbivores (i.e. native vs. introduced). Spines and thorns mainly affected the herbivores' selection of maximum twig sizes (reducing diameter and mass), but the minimum twig sizes selected were also reduced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47795/1/442_2004_Article_BF00317715.pd