DNA vaccines for emerging infectious diseases: what if?

A novel and powerful method for vaccine research, colloquially known as DNA vaccines, involves the deliberate introduction into tissues of a DNA plasmid carrying an antigen-coding gene that transfects cells in vivo and results in an immune response. DNA vaccines have several distinct advantages, which include ease of manipulation, use of a generic technology, simplicity of manufacture, and chemical and biological stability. In addition, DNA vaccines are a great leveler among re-searchers around the world because they provide unprecedented ease of experi-mentation. To facilitate diffusion of information, an Internet site has been established called THE DNA VACCINE WEB (URL:http://www.genweb.com/dnavax/dnavax.html). In this review, a brief survey is undertaken of the experimental models and preclinical work on DNA vaccines to contribute to a greater awareness of the possibilities for emerging infectious diseases

Radiation Hydrodynamical Instabilities in Cosmological and Galactic Ionization Fronts

Ionization fronts, the sharp radiation fronts behind which H/He ionizing photons from massive stars and galaxies propagate through space, were ubiquitous in the universe from its earliest times. The cosmic dark ages ended with the formation of the first primeval stars and galaxies a few hundred Myr after the Big Bang. Numerical simulations suggest that stars in this era were very massive, 25 - 500 solar masses, with H II regions of up to 30,000 light-years in diameter. We present three-dimensional radiation hydrodynamical calculations that reveal that the I-fronts of the first stars and galaxies were prone to violent instabilities, enhancing the escape of UV photons into the early intergalactic medium (IGM) and forming clumpy media in which supernovae later exploded. The enrichment of such clumps with metals by the first supernovae may have led to the prompt formation of a second generation of low-mass stars, profoundly transforming the nature of the first protogalaxies. Cosmological radiation hydrodynamics is unique because ionizing photons coupled strongly to both gas flows and primordial chemistry at early epochs, introducing a hierarchy of disparate characteristic timescales whose relative magnitudes can vary greatly throughout a given calculation. We describe the adaptive multistep integration scheme we have developed for the self-consistent transport of both cosmological and galactic ionization fronts.Comment: 6 pages, 4 figures, accepted for proceedings of HEDLA2010, Caltech, March 15 - 18, 201

Chronology: MSFC Space Station program, 1982 - present. Major events

The Marshall Space Flight Center (MSFC) maintains an active program to capture historical information and documentation on the MSFC's roles regarding Space Shuttle and Space Station. Marshall History Report 12, called Chronology: MSFC Space Station Program, 1982-Present, is presented. It contains synopses of major events listed according to the dates of their occurrence. Indices follow the synopses and provide additional data concerning the events listed. The Event Index provides a brief listing of all the events without synopses. The Element Index lists the specific elements of the Space Station Program under consideration in the events. The Location Index lists the locations where the events took place. The indices and synopses may be cross-referenced by using dates

Slush Hydrogen (SLH2) technology development for application to the National Aerospace Plane (NASP)

The National Aerospace Plane (NASP) program is giving us the opportunity to reach new unique answers in a number of engineering categories. The answers are considered enhancing technology or enabling technology. Airframe materials and densified propellants are examples of enabling technology. The National Aeronautics and Space Administration's Lewis Research Center has the task of providing the technology data which will be used as the basis to decide if slush hydrogen (SLH2) will be the fuel of choice for the NASP. The objectives of this NASA Lewis program are: (1) to provide, where possible, verified numerical models of fluid production, storage, transfer, and feed systems, and (2) to provide verified design criteria for other engineered aspects of SLH2 systems germane to a NASP. This program is a multiyear multimillion dollar effort. The present pursuit of the above listed objectives is multidimensional, covers a range of problem areas, works these to different levels of depth, and takes advantage of the resources available in private industry, academia, and the U.S. Government. The NASA Lewis overall program plan is summarized. The initial implementation of the plan will be unfolded and the present level of efforts in each of the resource areas will be discussed. Results already in hand will be pointed out. A description of additionally planned near-term experimental and analytical work is described

A Network Theory of Patentability

Patent law is built upon a fundamental premise: only significant inventions receive patent protection while minor improvements remain in the public domain. This premise is indispensable for maintaining an optimal balance between incentivizing new innovation and providing public access to existing innovation. Despite its importance, the doctrine that performs this gatekeeping role—nonobviousness— has long remained indeterminate and vague. Judicial opinions have struggled to articulate both what makes an invention significant (or nonobvious) and how to measure nonobviousness in specific cases. These difficulties are due in large part to the existence of two clashing theoretical frameworks, cognitive and economic, that have vied for prominence in justifying nonobviousness. Neither framework, however, has generated doctrinal tests that can be easily and consistently applied. This Article draws on a novel approach—network theory—to answer both the conceptual question (what is a nonobvious invention?) and the measurement question (how do we determine nonobviousness in specific cases?). First, it shows that what is missing in current conceptual definitions of nonobviousness is an underlying theory of innovation. It then supplies this missing piece. Building upon insights from network science, we model innovation as a process of search and recombination of existing knowledge. Distant searches that combine disparate or weakly connected portions of social and information networks tend to produce high-impact, new ideas that open novel innovation trajectories. Distant searches also tend to be costly and risky. In contrast, local searches tend to result in incremental innovation that is more routine, less costly, and less risky. From a network theory perspective, then, the goal of nonobviousness should be to reward, and therefore to incentivize, those risky distant searches and recombinations that produce the most socially significant innovations. By emphasizing factors specific to the structure of innovation—namely, the risks and costs of the search and recombination process—a network approach complements and deepens current economic understandings of nonobviousness. Second, based on our network theory of innovation, we develop an empirical, algorithmic measure of patentability—what we term a patent’s “network nonobviousness score” (NNOS). We harness data from US patent records to calculate the distance between the technical knowledge areas recombined in any given invention (or patent), allowing us to assign each patent a specific NNOS. We propose a doctrinal framework that incorporates an invention’s NNOS to nonobviousness determinations both at the examination phase and during patent litigation. Our use of network science to develop a legal algorithm is a methodological innovation in law, with implications for broader debates about computational law. We illustrate how differences in algorithm design can lead to different nonobviousness outcomes, and discuss how to mitigate the negative impact of black box algorithms

Toward the assessment of the susceptibility of a digital system to lightning upset

Accomplishments and directions for further research aimed at developing methods for assessing a candidate design of an avionic computer with respect to susceptability to lightning upset are reported. Emphasis is on fault tolerant computers. Both lightning stress and shielding are covered in a review of the electromagnetic environment. Stress characterization, system characterization, upset detection, and positive and negative design features are considered. A first cut theory of comparing candidate designs is presented including tests of comparative susceptability as well as its analysis and simulation. An approach to lightning induced transient fault effects is included

Spacelab energetic ion mass spectrometer

Basic design criteria are given for an ion mass spectrometer for use in studying magnetospheric ion populations. The proposed instrument is composed of an electrostatic analyzer followed by a magnetic spectrometer and simultaneously measures the energy per unit and mass per unit charge of the ion species. An electromagnet is used for momentum analysis to extend the operational energy range over a much wider domain than is possible with the permanent magnets used in previous flights. The energetic ion source regions, ion energization mechanisms, field line tracing, coordinated investigations, and orbit considerations are discussed and operations of the momentum analyzer and of the electrostatic energy analyzer are examined

Background, current status, and prognosis of the ongoing slush hydrogen technology development program for the NASP

Among the Hydrogen Projects at the NASA Lewis Research Center (NASA LeRC), is the task of implementing and managing the Slush Hydrogen (SLH2) Technology Program for the United States' National AeroSpace Plane Joint Program Office (NASP JPO). The objectives of this NASA LeRC program are to provide verified numerical models of fluid production, storage, transfer, and feed systems and to provide verified design criteria for other engineered aspects of SLH2 systems germane to a NASP. The pursuit of these objectives is multidimensional, covers a range of problem areas, works these to different levels of depth, and takes advantage of the resources available in private industry, academia, and the U.S. Government. A summary of the NASA LeRC overall SLH2 program plan, is presented along with its implementation, the present level of effort in each of the program areas, some of the results already in hand, and the prognosis for the effort in the immediate future

The Epstein-Barr Virus Episome Maneuvers between Nuclear Chromatin Compartments during Reactivation.

The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts on the EBV side localize to OriP, the latent origin of replication. This genetic element and the EBNA1 protein that binds there are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts on the human side localize to gene-poor and AT-rich regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of myriad interchromosomal associations also suggests a role for this type of long-range association in gene regulation.IMPORTANCE The human genome is structurally organized in three-dimensional space, and this structure functionally affects transcriptional activity. We set out to investigate whether a double-stranded DNA virus, Epstein-Barr virus (EBV), uses mechanisms similar to those of the human genome to regulate transcription. We found that the EBV genome associates with repressive compartments of the nucleus during latency and with active compartments during reactivation. This study advances our knowledge of the EBV life cycle, adding three-dimensional relocalization as a novel component to the molecular events that occur during reactivation. Furthermore, the data add to our understanding of nuclear compartments, showing that disperse interchromosomal interactions may be important for regulating transcription

Self-Reported Responses to Player Profile Questions Show Consistency with the Use of Complex Attentional Strategies by Expert Horseshoe Pitchers

The advantages on an external focus of attention have been demonstrated for a variety of sport tasks. The constrained action hypothesis (Wulf et al., 2001) argues that focusing externally on the movement effect results in the use of automated processes for movement control. In contrast, focusing internally in an attempt to control the movements of the body disrupts normally automated processes and degrades performance. Research on experts, however, suggests that they may adopt more complex attentional strategies. The present study provided a unique opportunity to examine expert horseshoe players’ attentional strategies as indicated by their self-reported responses to questions included in a National Horseshoe Pitchers Association (NHPA) player profile questionnaire. Responses submitted by 83 top NHPA players were examined to determine the frequency of references to the use of internal and external focus points and identify categories related to attentional strategies. Results indicated that the large majority of players reported using focus points that are consistent with an external focus of attention and that their thoughts corresponded to one or more categories related to technique, mental focus or concentration, general success, use of external focus cues, and emotional control. The findings are consistent with the view that experts may adopt complex attentional strategies that encompass both an external focus and thoughts about a variety of other performance related factors