A Model for Small Illinois School Districts in Response to Financial Crisis

This study describes the options available to small, rural Illinois school districts that face financial crises. The implications for a particular school relative to consolidation, annexation, cooperative high schools, tuitioning out, and tax referenda are described. Survey results relative to school effectiveness, the financial future, and school loyalty are reported and analyzed. The study concludes with a recommendation which appears most appropriate to solve the financial problems of the Findlay Community Unit School District #2

Low Seroprevalent Species D Adenovirus Vectors as Influenza Vaccines

Seasonal and pandemic influenza remains a constant threat. While standard influenza vaccines have great utility, the need for improved vaccine technologies have been brought to light by the 2009 swine flu pandemic, highly pathogenic avian influenza infections, and the most recent early and widespread influenza activity. Species C adenoviruses based on serotype 5 (AD5) are potent vehicles for gene-based vaccination. While potent, most humans are already immune to this virus. In this study, low seroprevalent species D adenoviruses Ad26, 28, and 48 were cloned and modified to express the influenza virus A/PR/8/34 hemagglutinin gene for vaccine studies. When studied in vivo, these species D Ad vectors performed quite differently as compared to species C Ad vectors depending on the route of immunization. By intramuscular injection, species D vaccines were markedly weaker than species C vaccines. In contrast, the species D vaccines were equally efficient as species C when delivered mucosally by the intranasal route. Intranasal adenovirus vaccine doses as low as 108 virus particles per mouse induced complete protection against a stringent lethal challenge dose of influenza. These data support translation of species D adenoviruses as mucosal vaccines and highlight the fundamental effects of differences in virus tropism on vaccine applications

Velocity-resolved observations of water in Comet Halley

High resolution (lambda/delta lambda approx. = 3 x 10 to the 5th power) near-infrared observations of H2O emission from Comet Halley were acquired at the time of maximum post-perihelion geocentric Doppler shift. The observed widths and absolute positions of the H2O line profiles reveal characteristics of the molecular velocity field in the coma. These results support H2O outflow from a Sun-lit hemisphere or the entire nucleus, but not from a single, narrow jet emanating from the nucleus. The measured pre- and post-perihelion outflow velocities were 0.9 + or - 0.2 and 1.4 + or - 0.2 km/s, respectively. Temporal variations in the kinematic properties of the outflow were inferred from changes in the spectral line shapes. These results are consistent with the release of H2O into the coma from multiple jets

Imaging Luciferase-expressing Viruses

Optical imaging of luciferage gene expression has become a powerful tool to track cells and viruses in vivo in small animal models. Luciferase imaging has been used to study the location of infection by replication-defective and replication-competent viruses and to track changes in the distribution of viruses in mouse models. This approach has also been used in oncolytic studies as a non-invasive means to monitor the growth and killing of tumor cells modified with luciferase genes. In this chapter, we describe the techniques used for luciferase imaging as have been applied to track replication-defective and replication-competent adenoviruses in mouse and hamster models of oncolysis and virus pharmacology. Although these methods are simple, the process of obtaining accurate luciferase imaging data has many caveats that will be discussed

GALEX Observations of CS and OH Emission in Comet 9P/Tempel 1 During Deep Impact

GALEX observations of comet 9P/Tempel 1 using the near ultraviolet (NUV) objective grism were made before, during and after the Deep Impact event that occurred on 2005 July 4 at 05:52:03 UT when a 370 kg NASA spacecraft was maneuvered into the path of the comet. The NUV channel provides usable spectral information in a bandpass covering 2000 - 3400 A with a point source spectral resolving power of approximately 100. The primary spectral features in this range include solar continuum scattered from cometary dust and emissions from OH and CS molecular bands centered near 3085 and 2575 A, respectively. In particular, we report the only cometary CS emission detected during this event. The observations allow the evolution of these spectral features to be tracked over the period of the encounter. In general, the NUV emissions observed from Tempel 1 are much fainter than those that have been observed by GALEX from other comets. However, it is possible to derive production rates for the parent molecules of the species detected by GALEX in Tempel 1 and to determine the number of these molecules liberated by the impact. The derived quiescent production rates are Q(H2O) = 6.4e27 molecules/s and Q(CS2) = 6.7e24 molecules/s, while the impact produced an additional 1.6e32 H2O molecules and 1.3e29 CS2 molecules, a similar ratio as in quiescent outgassing.Comment: 15 pages, 4 figures, accepted for publication in the Astrophysical Journa

A Novel Codon-optimized SIV Gag-pol Immunogen for Genebased Vaccination

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells resulting in poor expression of unmodified SIV genes. To provide a better SIV gag-pol immunogen for gene-based vaccination, we codon-optimized the full gag-pol sequence from SIVmac239. To increase pol expression, we artificially moved the pol sequence in frame to gag to bypass the need for a translational frame shift for its expression. Finally, we inserted four self-cleaving picornavirus sequences into gag p24, protease, reverse transcriptase, and into integrase to fragment the proteins for potentially better immune presentation. We demonstrate that these immunogens are well expressed in vitro and drive similar antibody and T cell responses with or without cleavage sequences

Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology is deduced from the most commonly used serotypes, Ad5 and Ad2. However, these serotypes may not represent all adenoviruses, and may not even represent the most useful vectors for all purposes. Chimeras between Ad serotypes may become useful in engineering vectors that can selectively evade substantial viral traps, such as Kupffer cells, while retaining the robust qualities of Ad5. Similarly, vectorizing other Ad serotypes may become useful in avoiding immunity against Ad5 altogether. Taken together, this research on basic adenovirus biology will be necessary in developing vectors that interact more strategically with the host for the most optimal therapeutic effect

A Novel Codon-optimized SIV Gag-pol Immunogen for Genebased Vaccination

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells resulting in poor expression of unmodified SIV genes. To provide a better SIV gag-pol immunogen for gene-based vaccination, we codon-optimized the full gag-pol sequence from SIVmac239. To increase pol expression, we artificially moved the pol sequence in frame to gag to bypass the need for a translational frame shift for its expression. Finally, we inserted four self-cleaving picornavirus sequences into gag p24, protease, reverse transcriptase, and into integrase to fragment the proteins for potentially better immune presentation. We demonstrate that these immunogens are well expressed in vitro and drive similar antibody and T cell responses with or without cleavage sequences

A Novel Codon-optimized SIV Gag-pol Immunogen for Genebased Vaccination

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells resulting in poor expression of unmodified SIV genes. To provide a better SIV gag-pol immunogen for gene-based vaccination, we codon-optimized the full gag-pol sequence from SIVmac239. To increase pol expression, we artificially moved the pol sequence in frame to gag to bypass the need for a translational frame shift for its expression. Finally, we inserted four self-cleaving picornavirus sequences into gag p24, protease, reverse transcriptase, and into integrase to fragment the proteins for potentially better immune presentation. We demonstrate that these immunogens are well expressed in vitro and drive similar antibody and T cell responses with or without cleavage sequences

CD46-Mediated Transduction of a Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines