INCITS W1.1 Standards for Perceptual Evaluation of Text and Line Quality

INCITS W1.1 is a project chartered to develop an appearance-based image quality standard. This paper summarizes the work to date of the W1.1 Text and Line Quality ad hoc team, and describes the progress made in developing a Text Quality test pattern and an analysis procedure based on experience with previous perceptual rating experiments

The California Current System: A multiscale overview and the development of a feature-oriented regional modeling system (FORMS)

17 USC 105 interim-entered record; under review.Over the past decade, the feature-oriented regional modeling methodology has been developed and applied in several ocean domains, including the western North Atlantic and tropical North Atlantic. This methodology is model-independent and can be utilized with or without satellite and/or in situ observations. Here we develop new feature-oriented models for the eastern North Pacific from 36◦ to 48◦N – essentially, most of the regional eastern boundary current. This is the firsttime feature-modeling has been applied to a complex eastern boundary current system. As a prerequisite to feature modeling, prevalent features that comprise the multiscale and complex circulation in the California Current system (CCS) are first overviewed. This description is based on contemporary understanding ofthe features and their dominant space and time scales of variability. A synergistic configuration of circulation features interacting with one another on multiple and sometimes overlapping space and time scales as a meander-eddy-upwelling system is presented. The second step is to define the feature-oriented regional modeling system (FORMS). The major multiscale circulation features include the mean flow and southeastward meandering jet(s) of the California Current (CC), the poleward flowing California Undercurrent (CUC), and six upwelling regions along the coastline. Next, the typical synoptic width, location, vertical extent, and core characteristics of these features and their dominant scales of variability are identified from past observational, theoretical and modeling studies. The parameterized features are then melded with the climatology, in situ and remotely sensed data, as available. The methodology is exemplified here for initialization of primitiveequation models. Dynamical simulations are run as nowcasts and short-term (4–6 weeks) forecasts using these feature models (FM) as initial fields and the Princeton Ocean Model (POM) for dynamics. The set of simulations over a 40-day period illustrate the applicability of FORMS to a transient eastern boundary current region such as the CCS. Comparisons are made with simulations initialized from climatology only. The FORMS approach increases skill in severalfactors, including the: (i) maintenance of the low-salinity pool in the core of the CC; (ii) representation of eddy activity inshore of the coastal transition zone; (iii) realistic eddy kinetic energy evolution; (iv) subsurface (intermediate depth) mesoscale feature evolution; and (v) deep poleward flow evolution.This work was funded by the Office of Naval Research grants N00014-03-1-0411 and N00014-03-1-0206 at the University of Massachusetts at Dartmouth. Leslie Rosenfeld’s participation was supported by ONR grant N00014-03-WR-20009. PFJL, PJH and WGL are grateful to ONR for support under grant N00014-08-1-1097, N00014-08-1-0680 and MURI-ASAP to the Massachusetts Institute of Technology

Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice

Acknowledgements We would like to thank the Biological Services Facility at the University of Manchester for expert animal husbandry and Karen Davies who helped with the MRI. The Histology Facility equipment that was used in this study was purchased by the University of Manchester Strategic Fund. Special thanks goes to Peter Walker for their help with the histology. Funding information This work was supported by the Kohn Foundation, an Edward Bonham Carter Doctoral Scholarship, an EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine studentship grant (EP/L014904/1), and the Medical Research Council (MR/K501311/1).Peer reviewedPublisher PD

CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes

Accurate chromosome segregation demands efficient capture of microtubules by kinetochores and their conversion to stable bioriented attachments that can congress and then segregate chromosomes. An early event is the shedding of the outermost fibrous corona layer of the kinetochore following microtubule attachment. Centromere protein F (CENP-F) is part of the corona, contains two microtubule-binding domains, and physically associates with dynein motor regulators. Here, we have combined CRISPR gene editing and engineered separation-of-function mutants to define how CENP-F contributes to kinetochore function. We show that the two microtubule-binding domains make distinct contributions to attachment stability and force transduction but are dispensable for chromosome congression. We further identify a specialized domain that functions to limit the dynein-mediated stripping of corona cargoes through a direct interaction with Nde1. This antagonistic activity is crucial for maintaining the required corona composition and ensuring efficient kinetochore biorientation

Selective liposomal transport through blood brain barrier disruption in ischaemic stroke reveals two distinct therapeutic opportunities

The development of effective therapies for stroke continues to face repeated translational failures. Brain endothelial cells form paracellular and transcellular barriers to many blood-borne therapies and the development of efficient delivery strategies is highly warranted. Here, in a mouse model of stroke, we show selective recruitment of clinically used liposomes into the ischaemic brain that correlates with biphasic blood brain barrier (BBB) breakdown. Intravenous administration of liposomes into mice exposed to transient middle cerebral artery occlusion took place at early (0.5h and 4h) and delayed (24h and 48h) timepoints, covering different phases of BBB disruption after stroke. Using a combination of in vivo real-time imaging and histological analysis we show that selective liposomal brain accumulation coincides with biphasic enhancement in transcellular transport followed by a delayed impairment to the paracellular barrier. This process precedes neurological damage in the acute phase and maintains long-term liposomal co-localisation within the neurovascular unit, which could have great potential for neuroprotection. Levels of liposomal uptake by glial cells are similarly selectively enhanced in the ischaemic region late after experimental stroke (2-3 days), highlighting their potential for blocking delayed inflammatory responses or shifting the polarization of microglia/macrophages towards brain repair. These findings demonstrate the capability of liposomes to maximise selective translocation into the brain after stroke and identify two windows for therapeutic manipulation. This emphasizes the benefits of selective drug delivery for efficient tailoring of stroke treatments

Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs

A search for quantitative trait loci controlling within-individual variation of physical activity traits in mice

<p>Abstract</p> <p>Background</p> <p>In recent years it has become increasingly apparent that physical inactivity can predispose individuals to a host of health problems. While many studies have analyzed the effect of various environmental factors on activity, we know much less about the genetic control of physical activity. Some studies in mice have discovered quantitative trait loci (QTL) influencing various physical activity traits, but mostly have analyzed inter-individual variation rather than variation in activity within individuals over time. We conducted a genome scan to identify QTLs controlling the distance, duration, and time run by mice over seven consecutive three-day intervals in an F₂population created by crossing two inbred strains (C57L/J and C3H/HeJ) that differed widely (average of nearly 300%) in their activity levels. Our objectives were (a) to see if we would find QTLs not originally discovered in a previous investigation that assessed these traits over the entire 21-day period and (b) to see if some of these QTLs discovered might affect the activity traits only in the early or in the late time intervals.</p> <p>Results</p> <p>This analysis uncovered 39 different QTLs, over half of which were new. Some QTLs affected the activity traits only in the early time intervals and typically exhibited significant dominance effects whereas others affected activity only in the later age intervals and exhibited less dominance. We also analyzed the regression slopes of the activity traits over the intervals, and found several QTLs affecting these traits that generally mapped to unique genomic locations.</p> <p>Conclusions</p> <p>It was concluded that the genetic architecture of physical activity in mice is much more complicated than has previously been recognized, and may change considerably depending on the age at which various activity measures are assessed.</p

A Bayesian Belief Network to assess rate of changes in coral reef ecosystems

It is crucial to identify sources of impacts and degradation to maintain functions and services that the physical structure of coral reef provides. Here, a Bayesian Network approach is used to evaluate effects that anthropogenic and climate change disturbances have on coral reef structure. The network was constructed on knowledge derived from the literature and elicited from experts, and parameterised on independent data. Evaluation of the model was conducted through sensitivity analyses and data integration was fundamental to obtain a balanced dataset. Scenario analyses, conducted to assess the effects of stressors on the reef framework state, suggested that calcifying organisms and carbonate production, rather than bioerosion, had the largest influence on the reef carbonate budgetary state. Despite the overall budget remaining positive, anthropogenic pressures, particularly deterioration of water quality, affected reef carbonate production, representing a warning signal for potential changes in the reef state

The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs