Plasticity of a critical antigenic determinant in the West Nile virus NY99 envelope protein domain III

West Nile virus (WNV) is a mosquito-borne flavivirus that causes febrile illness, encephalitis, and occasionally death in humans. The envelope protein is the main component of the WNV virion surface, and domain III of the envelope protein (EIII) is both a putative receptor binding domain and a target of highly specific, potently neutralizing antibodies. Envelope E-332 (E-332) is known to have naturally occurring variation and to be a key determinant of neutralization for anti-EIII antibodies. A panel of viruses containing all possible amino acid substitutions at E-332 was constructed. E-332 was found to be highly tolerant of mutation, and almost all of these changes had large impacts on antigenicity of EIII but only limited effects on growth or virulence phenotypes

Galactic Cosmic Ray Event-Based Risk Model (GERM) Code

This software describes the transport and energy deposition of the passage of galactic cosmic rays in astronaut tissues during space travel, or heavy ion beams in patients in cancer therapy. Space radiation risk is a probability distribution, and time-dependent biological events must be accounted for physical description of space radiation transport in tissues and cells. A stochastic model can calculate the probability density directly without unverified assumptions about shape of probability density function. The prior art of transport codes calculates the average flux and dose of particles behind spacecraft and tissue shielding. Because of the signaling times for activation and relaxation in the cell and tissue, transport code must describe temporal and microspatial density of functions to correlate DNA and oxidative damage with non-targeted effects of signals, bystander, etc. These are absolutely ignored or impossible in the prior art. The GERM code provides scientists data interpretation of experiments; modeling of beam line, shielding of target samples, and sample holders; and estimation of basic physical and biological outputs of their experiments. For mono-energetic ion beams, basic physical and biological properties are calculated for a selected ion type, such as kinetic energy, mass, charge number, absorbed dose, or fluence. Evaluated quantities are linear energy transfer (LET), range (R), absorption and fragmentation cross-sections, and the probability of nuclear interactions after 1 or 5 cm of water equivalent material. In addition, a set of biophysical properties is evaluated, such as the Poisson distribution for a specified cellular area, cell survival curves, and DNA damage yields per cell. Also, the GERM code calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle in a selected material. The GERM code makes the numerical estimates of basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the first option, properties of monoenergetic beams are treated. In the second option, the transport of beams in different materials is treated. Similar biophysical properties as in the first option are evaluated for the primary ion and its secondary particles. Additional properties related to the nuclear fragmentation of the beam are evaluated. The GERM code is a computationally efficient Monte-Carlo heavy-ion-beam model. It includes accurate models of LET, range, residual energy, and straggling, and the quantum multiple scattering fragmentation (QMSGRG) nuclear database

Recovery of West Nile Virus Envelope Protein Domain III Chimeras with Altered Antigenicity and Mouse Virulence

ABSTRACT Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras in vitro and in vivo revealed differences in growth and virulence between the viruses, with in vivo pathogenesis often not being correlated with in vitro growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence. IMPORTANCE The envelope (E) glycoprotein is the major protein present on the surface of flavivirus virions and is responsible for mediating virus binding and entry into target cells. Several viable West Nile virus (WNV) variants with chimeric E proteins in which the putative receptor-binding domain (EIII) sequences of other mosquito-borne flaviviruses were substituted in place of the WNV EIII were recovered, although the substitution of several more divergent EIII sequences was not tolerated. The differences in virulence and tissue tropism observed with the chimeric viruses indicate a significant role for this sequence in determining the pathogenesis of the virus within the mammalian host. Our studies demonstrate that these chimeras are viable and suggest that such recombinant viruses may be useful for investigation of domain-specific antibody responses and the more extensive definition of the contributions of EIII to the tropism and pathogenesis of WNV or other flaviviruses

Case Studies on the Implementation of Balanced Mix Design and Performance Tests for Asphalt Mixtures: California Department of Transportation (Caltrans)

The primary objective of this overall effort was to identify and put forth positive practices used by SHAs when implementing BMD and performance testing of asphalt mixtures. To accomplish this objective, information was collected through site visits and other means with seven key agencies. California Department of Transportation (Caltrans) graciously agreed to host a virtual site visit

Study of nuclear recoils in liquid argon with monoenergetic neutrons

For the development of liquid argon dark matter detectors we assembled a setup in the laboratory to scatter neutrons on a small liquid argon target. The neutrons are produced mono-energetically (E_kin=2.45 MeV) by nuclear fusion in a deuterium plasma and are collimated onto a 3" liquid argon cell operating in single-phase mode (zero electric field). Organic liquid scintillators are used to tag scattered neutrons and to provide a time-of-flight measurement. The setup is designed to study light pulse shapes and scintillation yields from nuclear and electronic recoils as well as from {\alpha}-particles at working points relevant to dark matter searches. Liquid argon offers the possibility to scrutinise scintillation yields in noble liquids with respect to the populations of the two fundamental excimer states. Here we present experimental methods and first results from recent data towards such studies.Comment: 9 pages, 8 figures, proceedings of TAUP 2011, to be published in Journal of Physics: Conference Series (JCPS

Case Studies on the Implementation of Balanced Mix Design and Performance Tests for Asphalt Mixtures: Illinois Department of Transportation (IDOT)

The primary objective of this overall effort was to identify and put forth positive practices used by SHAs when implementing BMD and performance testing of asphalt mixtures. To accomplish this objective, information was collected through site visits and other means with seven key agencies. Illinois Department of Transportation (IDOT) graciously agreed to host a virtual site visit

Case Studies on the Implementation of Balanced Mix Design and Performance Tests for Asphalt Mixtures: Texas Department of Transportation (TxDOT)

The primary objective of this overall effort was to identify and put forth positive practices used by SHAs when implementing BMD and performance testing of asphalt mixtures. To accomplish this objective, information was collected through site visits and other means with seven key agencies. Texas Department of Transportation (TxDOT) graciously agreed to host a virtual site visit

Positive Practices, Lessons Learned, and Challenges When Implementing Balanced Design of Asphalt Mixtures: Site Visits

Virtual site visits and interviews of seven key State Departments of Transportation (DOTs), along with material producers, consultants and paving contractors that serviced the agencies were conducted to learn more regarding the details of Balanced Mix Design (BMD) and performance tests implementation efforts. Successful practices documented from these virtual site visits were collected and synthesized into an overall process of implementing BMD as part of mix design approval and quality assurance (QA). This process comprises eight major tasks that are meant to present and summarize the activities that a State DOT may need to undertake to implement a BMD program depending on its organizational structure, staffing level, workspace, annual asphalt tonnage, as well as industry experiences and practices. Examples of positive practices, lessons learned, and challenges from States for the various tasks are presented. A list of research and deployment topics identified during the virtual site visits are also summarized

Case Studies on the Implementation of Balanced Mix Design and Performance Tests for Asphalt Mixtures: Maine Department of Transportation (MaineDOT)

The primary objective of this overall effort was to identify and put forth positive practices used by SHAs when implementing BMD and performance testing of asphalt mixtures. To accomplish this objective, information was collected through site visits and other means with seven key agencies. Maine Department of Transportation (MaineDOT) graciously agreed to host a virtual site visit