The Molecular Pathogenesis of Osteosarcoma: A Review

Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management

Progress toward curing HIV infection with hematopoietic cell transplantation.

HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT) from a graft that carried the HIV-resistant CCR5-∆32/∆32 mutation. Other attempts to establish a cure for HIV/AIDS using HCT in patients with HIV-1 and malignancy have yielded mixed results, as encouraging evidence for virus eradication in a few cases has been offset by poor clinical outcomes due to the underlying cancer or other complications. Such clinical strategies have relied on HIV-resistant hematopoietic stem and progenitor cells that harbor the natural CCR5-∆32/∆32 mutation or that have been genetically modified for HIV-resistance. Nevertheless, HCT with HIV-resistant cord blood remains a promising option, particularly with inventories of CCR5-∆32/∆32 units or with genetically modified, human leukocyte antigen-matched cord blood

Sensitivity of peatland litter decomposition to changes in temperature and rainfall

Changes to climate are projected over the next 50 years for many peatland areas. As decomposition of peatforming vegetation is likely to be intrinsically linked to these changes in climate, a clear understanding of climate-peat dynamics is required. There is concern that increased temperature and decreased precipitation could increase the rate of decomposition and put the carbon sink status of many peatlands at risk, yet few studies have examined the impact of both climatic factors together. To better understand the sensitivity of peatland decomposition to changes in both temperature and precipitation and their interaction, we conducted a shortterm laboratory experiment in which plant litters and peat soil were incubated, in isolation, in a factorial design. Treatments simulated baseline and projected climate averages derived from the latest UK climate change projections (UKCP09) for Exmoor, a climatically marginal peatland in SW England. Regular carbon dioxide flux measurements were made throughout the simulation, as well as total mass loss and total dissolved organic carbon (DOC) leached. The largest effect on carbon loss in this multifactor experiment was from substrate, with Sphagnum/peat releasing significantly less C in total during the experiment than dwarf shrubs/graminoids. Climate effects were substrate specific, with the drier rainfall treatment increasing the DOC leaching from Calluna, but decreasing it from Sphagnum. Partitioning between CO2 and DOC was also affected by climate, but only for the peat and Sphagnum samples, where the future climate scenarios (warmer and drier) resulted in a greater proportion of C lost in gaseous form. These results suggest that indirect effects of climate through changes in species composition in peatlands could ultimately turn out to be more important for litter decomposition than direct effects of climate change from increased temperatures and decreased rainfall

Linking changes in species composition and biomass in a globally distributed grassland experiment

Global change drivers, such as anthropogenic nutrient inputs, are increasing globally. Nutrient deposition simultaneously alters plant biodiversity, species composition and ecosystem processes like aboveground biomass production. These changes are underpinned by species extinction, colonisation and shifting relative abundance. Here, we use the Price equation to quantify and link the contributions of species that are lost, gained or that persist to change in aboveground biomass in 59 experimental grassland sites. Under ambient (control) conditions, compositional and biomass turnover was high, and losses (i.e. local extinctions) were balanced by gains (i.e. colonisation). Under fertilisation, the decline in species richness resulted from increased species loss and decreases in species gained. Biomass increase under fertilisation resulted mostly from species that persist and to a lesser extent from species gained. Drivers of ecological change can interact relatively independently with diversity, composition and ecosystem processes and functions such as aboveground biomass due to the individual contributions of species lost, gained or persisting.EEA Santa CruzFil: Ladouceur, Emma. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Ladouceur, Emma. Helmholtz Centre for Environmental Research – UFZ. Department of Physiological Diversity; AlemaniaFil: Ladouceur, Emma. University of Leipzig. Department of Biology; AlemaniaFil: Ladouceur, Emma. Martin Luther University Halle-Wittenberg. Institute of Computer Science; AlemaniaFil: Blowes, Shane A. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Blowes, Shane A. Martin Luther University Halle-Wittenberg. Institute of Computer Science; AlemaniaFil: Chase, Jonathan M. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Chase, Jonathan M. Martin Luther University Halle-Wittenberg. Institute of Computer Science; AlemaniaFil: Clark, Adam T. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Clark, Adam T. Helmholtz Centre for Environmental Research – UFZ. Department of Physiological Diversity; AlemaniaFil: Clark, Adam T. Karl-Franzens University of Graz. Institute of Biology; Austria.Fil: Garbowski, Magda. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Garbowski, Magda. Helmholtz Centre for Environmental Research – UFZ. Department of Physiological Diversity; AlemaniaFil: Alberti, Juan. Universidad Nacional de Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Laboratorio de Ecología. Mar del Plata; Argentina.Fil: Alberti, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Arnillas, Carlos Alberto. University of Toronto. Department of Physical and Environmental Sciences; Canadá.Fil: Bakker, Jonathan D. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Barrio, Isabel C. Agricultural University of Iceland. Faculty of Environmental and Forest Sciences; IslandiaFil: Bharath, Siddharth. Atria University; India.Fil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Harpole, Stanley. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Harpole, Stanley. Helmholtz Centre for Environmental Research – UFZ. Department of Physiological Diversity; AlemaniaMartin Luther University Halle-Wittenberg. Institute of Computer Science; Alemani

Metamodel-based model conformance and multiview consistency checking

Model-driven development, using languages such as UML and BON, often makes use of multiple diagrams (e.g., class and sequence diagrams) when modeling systems. These diagrams, presenting different views of a system of interest, may be inconsistent. A metamodel provides a unifying framework in which to ensure and check consistency, while at the same time providing the means to distinguish between valid and invalid models, that is, conformance. Two formal specifications of the metamodel for an object-oriented modeling language are presented, and it is shown how to use these specifications for model conformance and multiview consistency checking. Comparisons are made in terms of completeness and the level of automation each provide for checking multiview consistency and model conformance. The lessons learned from applying formal techniques to the problems of metamodeling, model conformance, and multiview consistency checking are summarized

Quasi-Periodic Occultation by a Precessing Accretion Disk and Other Variabilities of SMC X-1

We have investigated the variability of the binary X-ray pulsar, SMC X-1, in data from several X-ray observatories. We confirm the ~60-day cyclic variation of the X-ray flux in the long-term monitoring data from the RXTE and CGRO observatories. X-ray light curves and spectra from the ROSAT, Ginga, and ASCA observatories show that the uneclipsed flux varies by as much as a factor of twenty between a high-flux state when 0.71 second pulses are present and a low-flux state when pulses are absent. In contrast, during eclipses when the X-rays consist of radiation scattered from circumsource matter, the fluxes and spectra in the high and low states are approximately the same. These observations prove that the low state of SMC X-1 is not caused by a reduction in the intrinsic luminosity of the source, or a spectral redistribution thereof, but rather by a quasi-periodic blockage of the line of sight, most likely by a precessing tilted accretion disk. In each of two observations in the midst of low states a brief increase in the X-ray flux and reappearance of 0.71 second pulses occurred near orbital phase 0.2. These brief increases result from an opening of the line of sight to the pulsar that may be caused by wobble in the precessing accretion disk. The records of spin up of the neutron star and decay of the binary orbit are extended during 1991-1996 by pulse-timing analysis of ROSAT, ASCA, and RXTE PCA data. The pulse profiles in various energy ranges from 0.1 to >21 keV are well represented as a combination of a pencil beam and a fan beam. Finally, there is a marked difference between the power spectra of random fluctuations in the high-state data from the RXTE PCA below and above 3.4 keV. Deviation from the fitted power law around 0.06 Hz may be QPO.Comment: Accepted to ApJ. 33 pages including 11 figure