Multiscale Modeling of Influenza A Virus Infection Supports the Development of Direct-Acting Antivirals

Influenza A viruses are respiratory pathogens that cause seasonal epidemics with up to 500,000 deaths each year. Yet there are currently only two classes of antivirals licensed for treatment and drug-resistant strains are on the rise. A major challenge for the discovery of new anti-influenza agents is the identification of drug targets that efficiently interfere with viral replication. To support this step, we developed a multiscale model of influenza A virus infection which comprises both the intracellular level where the virus synthesizes its proteins, replicates its genome, and assembles new virions and the extracellular level where it spreads to new host cells. This integrated modeling approach recapitulates a wide range of experimental data across both scales including the time course of all three viral RNA species inside an infected cell and the infection dynamics in a cell population. It also allowed us to systematically study how interfering with specific steps of the viral life cycle affects virus production. We find that inhibitors of viral transcription, replication, protein synthesis, nuclear export, and assembly/release are most effective in decreasing virus titers whereas targeting virus entry primarily delays infection. In addition, our results suggest that for some antivirals therapy success strongly depends on the lifespan of infected cells and, thus, on the dynamics of virus-induced apoptosis or the host's immune response. Hence, the proposed model provides a systems-level understanding of influenza A virus infection and therapy as well as an ideal platform to include further levels of complexity toward a comprehensive description of infectious diseases

MODIS land cover and LAI Collection 4 product quality across nine sites in the western hemisphere

Global maps of land cover and leaf area index (LAI) derived from the Moderate Resolution Imaging Spectrometer (MODIS) reflectance data are an important resource in studies of global change, but errors in these must be characterized and well understood. Product validation requires careful scaling from ground and related measurements to a grain commensurate with MODIS products. We present an updated BigFoot project protocol for developing 25-m validation data layers over 49-km2 study areas. Results from comparisons of MODIS and BigFoot land cover and LAI products at nine contrasting sites are reported. In terms of proportional coverage, MODIS and BigFoot land cover were in close agreement at six sites. The largest differences were at low tree cover evergreen needleleaf sites and at an Arctic tundra site where the MODIS product overestimated woody cover proportions. At low leaf biomass sites there was reasonable agreement between MODIS and BigFoot LAI products, but there was not a particular MODIS LAI algorithm pathway that consistently compared most favorably. At high leaf biomass sites, MODIS LAI was generally overpredicted by a significant amount. For evergreen needleleaf sites, LAI seasonality was exaggerated by MODIS. Our results suggest incremental improvement from Collection 3 to Collection 4 MODIS products, with some remaining problems that need to be addresse

Treatment of infections of the lumbar spine with single-staged posterior instrumentation, disc debridement and interbody fusion with titanium cages

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Virtual constellations for global terrestrial monitoring

Free and open access to satellite imagery and value-added data products have revolutionized the role of remote sensing in Earth system science. Nonetheless, rapid changes in the global environment pose challenges to the science community that are increasingly difficult to address using data from single satellite sensors or platforms due to the underlying limitations of data availability and tradeoffs that govern the design and implementation of currently existing sensors. Virtual constellations of planned and existing satellite sensors may help to overcome this limitation by combining existing observations to mitigate limitations of any one particular sensor. While multi-sensor applications are not new, the integration and harmonization of multi-sensor data is still challenging, requiring tremendous efforts of science and operational user communities. Defined by the Committee on Earth Observation Satellites (CEOS) as a “set of space and ground segment capabilities that operate in a coordinated manner to meet a combined and common set of Earth Observation requirements”, virtual constellations can principally be used to combine sensors with similar spatial, spectral, temporal, and radiometric characteristics. We extend this definition to also include sensors that are principally incompatible, because they are fundamentally different (for instance active versus passive remote sensing systems), but their combination is necessary and beneficial to achieve a specific monitoring goal. In this case, constellations are more likely to build upon the complementarity of resultant information products from these incompatible sensors rather than the raw physical measurements. In this communication, we explore the potential and possible limitations to be overcome regarding virtual constellations for terrestrial science applications, discuss potentials and limitations of various candidate sensors, and provide context on integration of sensors. Thematically, we focus on land-cover and land-use change (LCLUC), with emphasis given to medium spatial resolution (i.e., pixels sided 10 to 100 m) sensors, specifically as a complement to those onboard the Landsat series of satellites. We conclude that virtual constellations have the potential to notably improve observation capacity and thereby Earth science and monitoring programs in general. Various national and international parties have made notable and valuable progress related to virtual constellations. There is, however, inertia inherent to Earth observation programs, largely related to their complexity, as well as national interests, observation aims, and high system costs. Herein we define and describe virtual constellations, offer the science and applications information needs to offer context, provide the scientific support for a range of virtual constellation levels based upon applications readiness, capped by a discussion of issues and opportunities toward facilitating implementation of virtual constellations (in their various forms).Crown Copyright © 2015 Published by Elsevier Inc. All rights reserved. This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/remote-sensing-of-environment/Keywords: Land cover, Monitoring, Landsat, Constellation, Sentinel-2, Satellite, Land use, Scienc

Balloon kyphoplasty in the treatment of metastatic disease of the spine: a 2-year prospective evaluation

There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety

The Interactive Effects of Ammonia and Microcystin on Life-History Traits of the Cladoceran Daphnia magna: Synergistic or Antagonistic?

The occurrence of Microcystis blooms is a worldwide concern that has caused numerous adverse effects on water quality and lake ecology. Elevated ammonia and microcystin concentrations co-occur during the degradation of Microcystis blooms and are toxic to aquatic organisms; we studied the relative and combined effects of these on the life history of the model organism Daphnia magna. Ammonia and microcystin-LR treatments were: 0, 0.366, 0.581 mg L−1 and 0, 10, 30, 100 µg L−1, respectively. Experiments followed a fully factorial design. Incubations were 14 d and recorded the following life-history traits: number of moults, time to first batch of eggs, time to first clutch, size at first batch of eggs, size at first clutch, number of clutches per female, number of offspring per clutch, and total offspring per female. Both ammonia and microcystin were detrimental to most life-history traits. Interactive effects of the toxins occurred for five traits: the time to first batch of eggs appearing in the brood pouch, time to first clutch, size at first clutch, number of clutches, and total offspring per female. The interactive effects of ammonia and microcystin appeared to be synergistic on some parameters (e.g., time to first eggs) and antagonistic on others (e.g., total offspring per female). In conclusion, the released toxins during the degradation of Microcystis blooms would result, according to our data, in substantially negative effect on D. magna

Comparison and assessment of coarse resolution land cover maps for Northern Eurasia

Information on land cover at global and continental scales is critical for addressing a range of ecological, socioeconomic and policy questions. Global land cover maps have evolved rapidly in the last decade, but efforts to evaluate map uncertainties have been limited, especially in remote areas like Northern Eurasia. Northern Eurasia comprises a particularly diverse region covering a wide range of climate zones and ecosystems: from arctic deserts, tundra, boreal forest, and wetlands, to semi-arid steppes and the deserts of Central Asia. In this study, we assessed four of the most recent global land cover datasets: GLC-2000, GLOBCOVER, and the MODIS Collection 4 and Collection 5 Land Cover Product using cross-comparison analyses and Landsat-based reference maps distributed throughout the region. A consistent comparison of these maps was challenging because of disparities in class definitions, thematic detail, and spatial resolution. We found that the choice of sampling unit significantly influenced accuracy estimates, which indicates that comparisons of reported global map accuracies might be misleading. To minimize classification ambiguities, we devised a generalized legend based on dominant life form types (LFT) (tree, shrub, and herbaceous vegetation, barren land and water). LFT served as a necessary common denominator in the analyzed map legends, but significantly decreased the thematic detail. We found significant differences in the spatial representation of LFT's between global maps with high spatial agreement (above 0.8) concentrated in the forest belt of Northern Eurasia and low agreement (below 0.5) concentrated in the northern taiga-tundra zone, and the southern dry lands. Total pixel-level agreement between global maps and six test sites was moderate to fair (overall agreement: 0.67-0.74, Kappa: 0.41-0.52) and increased by 0.09-0.45 when only homogenous land cover types were analyzed. Low map accuracies at our tundra test site confirmed regional disagreements and difficulties of current global maps in accurately mapping shrub and herbaceous vegetation types at the biome borders of Northern Eurasia. In comparison, tree dominated vegetation classes in the forest belt of the region were accurately mapped, but were slightly overestimated (10%-20%), in all maps. Low agreement of global maps in the northern and southern vegetation transition zones of Northern Eurasia is likely to have important implications for global change research, as those areas are vulnerable to both climate and socio-economic changes. (C) 2011 Elsevier Inc. All rights reserved.Keywords: Land cover, MODIS, Eurasia, Global, Validation, GLC-2000, LCCS, GLOBCOVERKeywords: Land cover, MODIS, Eurasia, Global, Validation, GLC-2000, LCCS, GLOBCOVE

A Molecular and Co-Evolutionary Context for Grazer Induced Toxin Production in Alexandrium tamarense

Marine dinoflagellates of the genus Alexandrium are the proximal source of neurotoxins associated with Paralytic Shellfish Poisoning. The production of these toxins, the toxin biosynthesis and, thus, the cellular toxicity can be influenced by abiotic and biotic factors. There is, however, a lack of substantial evidence concerning the toxins' ecological function such as grazing defense. Waterborne cues from copepods have been previously found to induce a species-specific increase in toxin content in Alexandrium minutum. However, it remains speculative in which context these species-specific responses evolved and if it occurs in other Alexandrium species as well. In this study we exposed Alexandrium tamarense to three copepod species (Calanus helgolandicus, Acartia clausii, and Oithona similis) and their corresponding cues. We show that the species-specific response towards copepod-cues is not restricted to one Alexandrium species and that co-evolutionary processes might be involved in these responses, thus giving additional evidence for the defensive role of phycotoxins. Through a functional genomic approach we gained insights into the underlying molecular processes which could trigger the different outcomes of these species-specific responses and consequently lead to increased toxin content in Alexandrium tamarense. We propose that the regulation of serine/threonine kinase signaling pathways has a major influence in directing the external stimuli i.e. copepod-cues, into different intracellular cascades and networks in A. tamarense. Our results show that A. tamarense can sense potential predating copepods and respond to the received information by increasing its toxin production. Furthermore, we demonstrate how a functional genomic approach can be used to investigate species interactions within the plankton community

Bringing an ecological view of change to Landsat-based remote sensing

When characterizing the processes that shape ecosystems, ecologists increasingly use the unique perspective offered by repeat observations of remotely sensed imagery. However, the concept of change embodied in much of the traditional remote-sensing literature was primarily limited to capturing large or extreme changes occurring in natural systems, omitting many more subtle processes of interest to ecologists. Recent technical advances have led to a fundamental shift toward an ecological view of change. Although this conceptual shift began with coarser-scale global imagery, it has now reached users of Landsat imagery, since these datasets have temporal and spatial characteristics appropriate to many ecological questions. We argue that this ecologically relevant perspective of change allows the novel characterization of important dynamic processes, including disturbances, long-term trends, cyclical functions, and feedbacks, and that these improvements are already facilitating our understanding of critical driving forces, such as climate change, ecological interactions, and economic pressures.This is the publisher’s final pdf. The published article is copyrighted by the Ecological Society of America and can be found at: http://www.esajournals.org/loi/fron.Keywords: Time-series, Forest disturbanc