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Bellevue, WA, United States

Many questions remain about P. falciparum within-host dynamics, immunity, and transmission-issues that may affect public health campaign planning. These gaps in knowledge concern the distribution of durations of malaria infections, determination of peak parasitemia during acute infection, the relationships among gametocytes and immune responses and infectiousness to mosquitoes, and the effect of antigenic structure on reinfection outcomes. The present model of intra-host dynamics of P. falciparum implements detailed representations of parasite and immune dynamics, with structures based on minimal extrapolations from first-principles biology in its foundations. The model is designed to quickly and readily accommodate gains in mechanistic understanding and to evaluate effects of alternative biological hypothesis through in silico experiments. Simulations follow the parasite from the liver-stage through the detailed asexual cycle to clearance while tracking gametocyte populations. The modeled immune system includes innate inflammatory and specific antibody responses to a repertoire of antigens. The mechanistic focus provides clear explanations for the structure of the distribution of infection durations through the interaction of antigenic variation and innate and adaptive immunity. Infectiousness to mosquitoes appears to be determined not only by the density of gametocytes but also by the level of inflammatory cytokines, which harmonizes an extensive series of study results. Finally, pre-existing immunity can either decrease or increase the duration of infections upon reinfection, depending on the degree of overlap in antigenic repertoires and the strength of the pre-existing immunity. © 2012 Philip Eckhoff. Source


Ma Y.,Intellectual Ventures
2015 15th Non-Volatile Memory Technology Symposium, NVMTS 2015 | Year: 2015

We propose a new memory hierarchy for energy conscious internet of things (IoT) integrated circuits. In this scheme a new type of SRAM cell - hybrid of SRAM/DRAM or SRAM/NVM memory - that is capable of storing multiple bits are used to bring caching to the bit level, near processor cores. This new scheme is expected to have energy efficiency advantage over traditional memory hierarchy for multi-context computation, especially suitable for many IoT applications. © 2015 IEEE. Source


Caldeira K.,Carnegie Institution | Myhrvold N.P.,Intellectual Ventures
Environmental Research Letters | Year: 2013

The temperature response of atmosphere-ocean climate models is analyzed based on atmospheric CO2 step-function-change simulations submitted to phase 5 of the Coupled Model Intercomparison Project (CMIP5). From these simulations and a control simulation, we estimate adjusted radiative forcing, the climate feedback parameter, and effective climate system thermal inertia, and we show that these results can be used to predict the temperature response to time-varying CO2 concentrations. We evaluate several kinds of simple mathematical models for the CMIP5 simulation results, including single- and multiple-exponential models and a one-dimensional ocean-diffusion model. All of these functional forms, except the single-exponential model, can produce curves that fit most CMIP5 results quite well for both continuous and step-function CO2-change pathways. Choice of model for any particular application would include consideration of factors such as the number of free parameters to be constrained and the conception of the underlying mechanistic model. Smooth curve fits to the CMIP5 simulation results realize approximately half (range 38%-61%) of equilibrium warming within the first decade after a CO2 concentration increase, but approximately one quarter (range 14%-40%) of equilibrium warming occurs more than a century after the CO 2 increase. Following an instantaneous quadrupling of atmospheric CO2, fits to four of the 20 simulation results reach 4 ° C of warming within the first decade, but fits to three of the 20 simulation results require more than a century to reach 4 ° C. These results indicate the need to reduce uncertainty in the temporal response of climate models and to consider this uncertainty when evaluating the risks posed by climate change. © 2013 IOP Publishing Ltd. Source


Ibrahim N.,University of Chicago | Sereno P.C.,University of Chicago | Sasso C.D.,Museo di Storia Naturale di Milan | Maganuco S.,Museo di Storia Naturale di Milan | And 5 more authors.
Science | Year: 2014

We describe adaptations for a semiaquatic lifestyle in the dinosaur Spinosaurus aegyptiacus. These adaptations include retraction of the fleshy nostrils to a position near the mid-region of the skull and an elongate neck and trunk that shift the center of body mass anterior to the knee joint. Unlike terrestrial theropods, the pelvic girdle is downsized, the hindlimbs are short, and all of the limb bones are solid without an open medullary cavity, for buoyancy control in water. The short, robust femur with hypertrophied flexor attachment and the low, flat-bottomed pedal claws are consistent with aquatic foot-propelled locomotion. Surface striations and bone microstructure suggest that the dorsal sail may have been enveloped in skin that functioned primarily for display on land and in water. Copyright 2014 by the American Association for the Advancement of Science; all rights reserved. Source


Myhrvold N.P.,Intellectual Ventures | Caldeira K.,Carnegie Institution
Environmental Research Letters | Year: 2012

A transition from the global system of coal-based electricity generation to low-greenhouse-gas-emission energy technologies is required to mitigate climate change in the long term. The use of current infrastructure to build this new low-emission system necessitates additional emissions of greenhouse gases, and the coal-based infrastructure will continue to emit substantial amounts of greenhouse gases as it is phased out. Furthermore, ocean thermal inertia delays the climate benefits of emissions reductions. By constructing a quantitative model of energy system transitions that includes life-cycle emissions and the central physics of greenhouse warming, we estimate the global warming expected to occur as a result of build-outs of new energy technologies ranging from 100GWe to 10TWe in size and 1100yr in duration. We show that rapid deployment of low-emission energy systems can do little to diminish the climate impacts in the first half of this century. Conservation, wind, solar, nuclear power, and possibly carbon capture and storage appear to be able to achieve substantial climate benefits in the second half of this century; however, natural gas cannot. © 2012 IOP Publishing Ltd. Source

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