Multiscale Toxicology- Building the Next Generation Tools for Toxicology

A Cooperative Research and Development Agreement (CRADA) was established between Battelle Memorial Institute (BMI), Pacific Northwest National Laboratory (PNNL), Oak Ridge National Laboratory (ORNL), Brookhaven National Laboratory (BNL), Lawrence Livermore National Laboratory (LLNL) with the goal of combining the analytical and synthetic strengths of the National Laboratories with BMI�s expertise in basic and translational medical research to develop a collaborative pipeline and suite of high throughput and imaging technologies that could be used to provide a more comprehensive understanding of material and drug toxicology in humans. The Multi-Scale Toxicity Initiative (MSTI), consisting of the team members above, was established to coordinate cellular scale, high-throughput in vitro testing, computational modeling and whole animal in vivo toxicology studies between MSTI team members. Development of a common, well-characterized set of materials for testing was identified as a crucial need for the initiative. Two research tracks were established by BMI during the course of the CRADA. The first research track focused on the development of tools and techniques for understanding the toxicity of nanomaterials, specifically inorganic nanoparticles (NPs). ORNL�s work focused primarily on the synthesis, functionalization and characterization of a common set of NPs for dissemination to the participating laboratories. These particles were synthesized to retain the same surface characteristics and size, but to allow visualization using the variety of imaging technologies present across the team. Characterization included the quantitative analysis of physical and chemical properties of the materials as well as the preliminary assessment of NP toxicity using commercially available toxicity screens and emerging optical imaging strategies. Additional efforts examined the development of high-throughput microfluidic and imaging assays for measuring NP uptake, localization, and toxicity in vitro. The second research track within the MSTI CRADA focused on the development of ex vivo animal models for examining druginduced cardiotoxicity. ORNL's role in the second track was limited initially, but was later expanded to include the development of microfluidic platforms that might facilitate the translation of Cardiac 'Microwire' technologies developed at the University of Toronto into a functional platform for drug screening and predictive assessment of cardiotoxicity via highthroughput measurements of contractility. This work was coordinated by BMI with the Centre for the Commercialization of Regenerative Medicine (CCRM) and the University of Toronto (U Toronto). This partnership was expanded and culminated in the submission of proposal to Work for Others (WFO) agencies to explore the development of a broader set of microphysiological systems, a so call human-on-a-chip, that could be used for toxicity screening and the evaluation of bio-threat countermeasures

The Cratering History of Asteroid (2867) Steins

The cratering history of main belt asteroid (2867) Steins has been investigated using OSIRIS imagery acquired during the Rosetta flyby that took place on the 5th of September 2008. For this purpose, we applied current models describing the formation and evolution of main belt asteroids, that provide the rate and velocity distributions of impactors. These models coupled with appropriate crater scaling laws, allow the cratering history to be estimated. Hence, we derive Steins' cratering retention age, namely the time lapsed since its formation or global surface reset. We also investigate the influence of various factors -like bulk structure and crater erasing- on the estimated age, which spans from a few hundred Myrs to more than 1Gyr, depending on the adopted scaling law and asteroid physical parameters. Moreover, a marked lack of craters smaller than about 0.6km has been found and interpreted as a result of a peculiar evolution of Steins cratering record, possibly related either to the formation of the 2.1km wide impact crater near the south pole or to YORP reshaping.Comment: Accepted by Planetary and Space Scienc

Physical Investigation of the Potentially Hazardous Asteroid (144898) 2004 VD17

In this paper we present the observational campaign carried out at ESO NTT and VLT in April and May 2006 to investigate the nature and the structure of the Near Earth Object (144898) 2004 VD17. In spite of a great quantity of dynamical information, according to which it will have a close approach with the Earth in the next century, the physical properties of this asteroid are largely unknown. We performed visible and near--infrared photometry and spectroscopy, as well as polarimetric observations. Polarimetric and spectroscopic data allowed us to classify 2004 VD17 as an E-type asteroid. A good agreement was also found with the spectrum of the aubrite meteorite Mayo Belwa. On the basis of the polarimetric albedo (p_v=0.45) and of photometric data, we estimated a diameter of about 320 m and a rotational period of about 2 hours. The analysis of the results obtained by our complete survey have shown that (144898) 2004 VD17 is a peculiar NEO, since it is close to the breakup limits for fast rotator asteroids, as defined by Pravec and Harris (2000). These results suggest that a more robust structure must be expected, as a fractured monolith or a rubble pile in a "strength regime" (Holsapple 2002).Comment: 32 pages, 7 figure, paper accepted for publication in Icaru

Generalized h-index for Disclosing Latent Facts in Citation Networks

What is the value of a scientist and its impact upon the scientific thinking? How can we measure the prestige of a journal or of a conference? The evaluation of the scientific work of a scientist and the estimation of the quality of a journal or conference has long attracted significant interest, due to the benefits from obtaining an unbiased and fair criterion. Although it appears to be simple, defining a quality metric is not an easy task. To overcome the disadvantages of the present metrics used for ranking scientists and journals, J.E. Hirsch proposed a pioneering metric, the now famous h-index. In this article, we demonstrate several inefficiencies of this index and develop a pair of generalizations and effective variants of it to deal with scientist ranking and with publication forum ranking. The new citation indices are able to disclose trendsetters in scientific research, as well as researchers that constantly shape their field with their influential work, no matter how old they are. We exhibit the effectiveness and the benefits of the new indices to unfold the full potential of the h-index, with extensive experimental results obtained from DBLP, a widely known on-line digital library.Comment: 19 pages, 17 tables, 27 figure

Evaluation of ontology enhancement tools

Mining algorithms can enhance the task of ontology establishment but methods are needed to assess the quality of their findings. Ontology establishment is a long-term interactive process, so it is important to evaluate the contribution of a mining tool at an early phase of this process so that only appropriate tools are used in later phases. We propose a method for the evaluation of such tools on their impact on ontology enhancement. We model impact as quality perceived by the expert and as statistical quality computed by an objective function. We further provide a mechanism that juxtaposes the two forms of quality. We have applied our method on an ontology enhancement tool and gained some interesting insights on the interplay between perceived impact and statistical quality. © 2006 Springer-Verlag

E-government adoption: A cultural comparison

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008.E-government diffusion is an international phenomenon. This study compares e-government adoption in the U.K. to adoption in the U.S. In particular, this study seeks to determine if the same factors are salient in both countries. Several studies have explored citizen acceptance of e-government services in the U.S. However, few studies have explored this phenomenon in the U.K. To identify the similarities and differences between the U.K. and the U.S. a survey is conducted in the U.K. and the findings are compared to the literature that investigates diffusion in the U.S. This study proposes a model of e-government adoption in the U.K. based on salient factors in the U.S. A survey is administered to 260 citizens in London to assess the importance of relative advantage, trust and the digital divide on intention to use e-government. The results of binary logistic regression indicate that there are cultural differences in e-government adoption in the U.K. and the U.S. The results indicate that of the prevailing adoption constructs, relative advantage and trust are pertinent in both the U.S. and the U.K., while ICT adoption barriers such as access and skill may vary by culture. Implications for research and practice are discussed

Cohesive forces prevent the rotational breakup of rubble-pile asteroid (29075) 1950 DA

Space missions and ground-based observations have shown that some asteroids are loose collections of rubble rather than solid bodies. The physical behaviour of such ‘rubble-pile’ asteroids has been traditionally described using only gravitational and frictional forces within a granular material. Cohesive forces in the form of small van der Waals forces between constituent grains have recently been predicted to be important for small rubble piles (ten kilometres across or less), and could potentially explain fast rotation rates in the small-asteroid population. The strongest evidence so far has come from an analysis of the rotational breakup of the main-belt comet P/2013 R3, although that was indirect and poorly constrained by observations. Here we report that the kilometre-sized asteroid (29075) 1950 DA is a rubble pile that is rotating faster than is allowed by gravity and friction. We find that cohesive forces are required to prevent surface mass shedding and structural failure, and that the strengths of the forces are comparable to, though somewhat less than, the forces found between the grains of lunar regolith

Asteroids. From Observations to Models

We will discuss some specific applications to the rotation state and the shapes of moderately large asteroids, and techniques of observations putting some emphasis on the HST/FGS instrument.Comment: to appear in LNP; 28pages; written in 2003; Winter School "Dynamique des Corps Celestes Non Ponctuels et des Anneaux", Lanslevillard (FRANCE

Tidal Evolution of Close Binary Asteroid Systems

We provide a generalized discussion of tidal evolution to arbitrary order in the expansion of the gravitational potential between two spherical bodies of any mass ratio. To accurately reproduce the tidal evolution of a system at separations less than five times the radius of the larger primary component, the tidal potential due to the presence of a smaller secondary component is expanded in terms of Legendre polynomials to arbitrary order rather than truncated at leading order as is typically done in studies of well-separated system like the Earth and Moon. The equations of tidal evolution including tidal torques, the changes in spin rates of the components, and the change in semimajor axis (orbital separation) are then derived for binary asteroid systems with circular and equatorial mutual orbits. Accounting for higher-order terms in the tidal potential serves to speed up the tidal evolution of the system leading to underestimates in the time rates of change of the spin rates, semimajor axis, and mean motion in the mutual orbit if such corrections are ignored. Special attention is given to the effect of close orbits on the calculation of material properties of the components, in terms of the rigidity and tidal dissipation function, based on the tidal evolution of the system. It is found that accurate determinations of the physical parameters of the system, e.g., densities, sizes, and current separation, are typically more important than accounting for higher-order terms in the potential when calculating material properties. In the scope of the long-term tidal evolution of the semimajor axis and the component spin rates, correcting for close orbits is a small effect, but for an instantaneous rate of change in spin rate, semimajor axis, or mean motion, the close-orbit correction can be on the order of tens of percent.Comment: 40 pages, 2 tables, 8 figure