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Joan Flasch Artists' Book Collection

Francisella tularensis subspecies tularensis is an extremely virulent facultative intracellular bacterial pathogen capable of causing significant mortality in humans when inhaled. Consequently, subspecies tularensis was developed as a biological weapon more than 50 years ago. To counter this threat the US Army empirically developed a live vaccine strain, F. tularensis LVS, from the less virulent holarctica subspecies. In human experiments LVS afforded substantial protection against transdermal challenge with clinical subspecies tularensis strain, SCHU S4, but lesser protection against infection initiated by inhalation of the pathogen. Several regulatory and clinical issues remain unresolved for this vaccine, including the absence of a robust correlate of protection. To try to address this, we have developed several defined gene deletion mutants of SCHU S4 that elicit varying degrees of protection in a mouse dermal or respiratory challenge model. In the present study, we have examined whether host immune responses to immunization with such live vaccine candidates can serve as correlates of protection. Antibody responses were unable to distinguish between effective and ineffective vaccine strains. However, several cytokine responses to vaccination showed some promise. Especially, serum levels of TNFα, IFNγ, and MCP-1 between days 4 and 7 after vaccination appear to correlate with protection against respiratory challenge.

Francisella tularensis subspecies tularensis is highly virulent for humans especially when it is inhaled. Therefore, it has the potential to be used as a biothreat agent. Vaccines against F. tularensis will need to be approved in accordance with the FDA Animal Rule. This will require identification of robust correlates of protection in experimental animals and the demonstration that similar immune responses are generated in vaccinated humans. Towards this goal, we have developed an experimental live vaccine strain by deleting the gene, clpB, encoding a heat shock protein from virulent subsp. tularensis strain, SCHU S4. SCHU S4 Delta clpB administered intradermally protects BALB/c, but not C57BL/6 mice from subsequent respiratory challenge with wildtype SCHU S4. A comparison of post-vaccination and post-challenge immune responses in these two mouse strains shows an association between several antibody and cytokine responses and protection. In particular, elevated IFN gamma levels in the skin 2 days after vaccination, sero-conversion to hypothetical membrane protein ETT_778c, and to 30S ribosomal protein Si (FTT_0183c) of F. tularensis after 30 days of vaccination, and elevated levels of pulmonary IL-17 on day 7 after respiratory challenge with SCHU S4 were all associated with protection. (C) 2012 Wayne Conlan. Published by Elsevier Ltd. All rights reserved.

This is the first report characterizing local and systemic cytokine and chemokine responses in mice immunized with vaccines with different efficacies against aerosol challenge with virulent F. tularensis subsp. tularensis. It shows that increases in the levels of most of these immunomodulators, including those known to be critical for protective immunity, do not superficially correlate with protection unless adjusted for the effects of bacterial burden. Additionally, several cytokines were selectively suppressed in the lungs of naïve mice, suggesting that one mechanism of vaccine action is to overcome this pathogen-induced immunosuppression.

This is the first report characterizing local and systemic cytokine and chemokine responses in mice immunized with vaccines with different efficacies against aerosol challenge with virulent F. tularensis subsp. tularensis. It shows that increases in the levels of most of these immunomodulators, including those known to be critical for protective immunity, do not superficially correlate with protection unless adjusted for the effects of bacterial burden. Additionally, several cytokines were selectively suppressed in the lungs of naïve mice, suggesting that one mechanism of vaccine action is to overcome this pathogen-induced immunosuppression.

This is the first report characterizing local and systemic cytokine and chemokine responses in mice immunized with vaccines with different efficacies against aerosol challenge with virulent F. tularensis subsp. tularensis. It shows that increases in the levels of most of these immunomodulators, including those known to be critical for protective immunity, do not superficially correlate with protection unless adjusted for the effects of bacterial burden. Additionally, several cytokines were selectively suppressed in the lungs of naïve mice, suggesting that one mechanism of vaccine action is to overcome this pathogen-induced immunosuppression.

This is the first report characterizing local and systemic cytokine and chemokine responses in mice immunized with vaccines with different efficacies against aerosol challenge with virulent F. tularensis subsp. tularensis. It shows that increases in the levels of most of these immunomodulators, including those known to be critical for protective immunity, do not superficially correlate with protection unless adjusted for the effects of bacterial burden. Additionally, several cytokines were selectively suppressed in the lungs of naïve mice, suggesting that one mechanism of vaccine action is to overcome this pathogen-induced immunosuppression.

This is the first report characterizing local and systemic cytokine and chemokine responses in mice immunized with vaccines with different efficacies against aerosol challenge with virulent F. tularensis subsp. tularensis. It shows that increases in the levels of most of these immunomodulators, including those known to be critical for protective immunity, do not superficially correlate with protection unless adjusted for the effects of bacterial burden. Additionally, several cytokines were selectively suppressed in the lungs of naïve mice, suggesting that one mechanism of vaccine action is to overcome this pathogen-induced immunosuppression.

The type A subspecies of Francisella tularensis is a highly virulent facultative intracellular bacterial pathogen, and a potential biological weapon. Recently, there has been renewed interest in developing new vaccines and therapeutics against this bacterium. Natural cases of disease, tularemia, caused by the type A subspecies are very rare. Therefore, the United States Food and Drug Administration will rely on the so-called Animal Rule for efficacy testing of anti-Francisella medicines. This requires the human disease to be modeled in one or more animal species in which the pathogenicity of the agent is reasonably well understood. Mice are natural hosts for F. tularensis, and might be able to satisfy this requirement. Tularemia pathogenesis appears to be primarily due to the host inflammatory response which is poorly understood at the molecular level. Additionally, the extent to which this response varies depending on host and pathogen genetic background, or by pathogen challenge route or dose is unknown. Therefore, the present study examined sera and infected tissues from C57BL/6 and BALB/c mice challenged by natural intradermal (ID) and respiratory routes with one of two distinct type A strains of the pathogen for cytokine and chemokine responses that might help to explain the morbidity associated with tularemia. The results show that the molecular immune response was mostly similar regardless of the variables examined. For instance, mRNA for the proinflammatory cytokine IL-6, and chemokines KC, and IP-10 was consistently upregulated at all sites of infection. Upregulation of mRNA for several other cytokines and chemokines occurred in a more tissue restricted manner. For instance, IFN-gamma was highly upregulated in the skin of BALB/c, but not C57BL/6 mice after ID inoculation of the pathogen, whilst IL-10 mRNA upregulation was only consistently seen in the skin and lungs.

The type A subspecies of Francisella tularensis is a highly virulent facultative intracellular bacterial pathogen, and a potential biological weapon. Recently, there has been renewed interest in developing new vaccines and therapeutics against this bacterium. Natural cases of disease, tularemia, caused by the type A subspecies are very rare. Therefore, the United States Food and Drug Administration will rely on the so-called Animal Rule for efficacy testing of anti-Francisella medicines. This requires the human disease to be modeled in one or more animal species in which the pathogenicity of the agent is reasonably well understood. Mice are natural hosts for F. tularensis, and might be able to satisfy this requirement. Tularemia pathogenesis appears to be primarily due to the host inflammatory response which is poorly understood at the molecular level. Additionally, the extent to which this response varies depending on host and pathogen genetic background, or by pathogen challenge route or dose is unknown. Therefore, the present study examined sera and infected tissues from C57BL/6 and BALB/c mice challenged by natural intradermal (ID) and respiratory routes with one of two distinct type A strains of the pathogen for cytokine and chemokine responses that might help to explain the morbidity associated with tularemia. The results show that the molecular immune response was mostly similar regardless of the variables examined. For instance, mRNA for the proinflammatory cytokine IL-6, and chemokines KC, and IP-10 was consistently upregulated at all sites of infection. Upregulation of mRNA for several other cytokines and chemokines occurred in a more tissue restricted manner. For instance, IFN-gamma was highly upregulated in the skin of BALB/c, but not C57BL/6 mice after ID inoculation of the pathogen, whilst IL-10 mRNA upregulation was only consistently seen in the skin and lungs.

The wavelength and Einstein A coefficient are calculated for all rotation-vibration transitions of $^4$He$^1$H$^+$, $^3$He$^1$H$^+$, $^4$He$^2$H$^+$ and $^3$He$^2$H$^+$, giving a complete line list and the partition function for $^4$HeH$^+$ and its isotopologues. This opacity is included in the calculation of the total opacity of low-metallicity stars and its effect is analysed for different conditions of temperature, density and hydrogen number fraction. For a low helium number fraction (as in the Sun), it is found that HeH$^+$ has a visible but small effect for very low densities ($\rho\leq 10^{-10}$g cm$^{-3}$), at temperatures around 3500 K. However, for high helium number fraction, the effect of HeH$^+$ becomes important for higher densities ($\rho\leq 10^{-6}$g cm$^{-3}$), its effect being most important for a temperature around 3500 K. Synthetic spectra for a variety of different conditions are presented., Comment: 8 pages, 2 Figures Accepted for publication in Mon.Not.Roy.Astron.Soc

The wavelength and Einstein A coefficient are calculated for all rotation-vibration transitions of $^4$He$^1$H$^+$, $^3$He$^1$H$^+$, $^4$He$^2$H$^+$ and $^3$He$^2$H$^+$, giving a complete line list and the partition function for $^4$HeH$^+$ and its isotopologues. This opacity is included in the calculation of the total opacity of low-metallicity stars and its effect is analysed for different conditions of temperature, density and hydrogen number fraction. For a low helium number fraction (as in the Sun), it is found that HeH$^+$ has a visible but small effect for very low densities ($\rho\leq 10^{-10}$g cm$^{-3}$), at temperatures around 3500 K. However, for high helium number fraction, the effect of HeH$^+$ becomes important for higher densities ($\rho\leq 10^{-6}$g cm$^{-3}$), its effect being most important for a temperature around 3500 K. Synthetic spectra for a variety of different conditions are presented., Comment: 8 pages, 2 Figures Accepted for publication in Mon.Not.Roy.Astron.Soc

NLS-SCHOLAR is a prototype system that uses Artificial Intelligence techniques to teach computer-naive people how to use a powerful and complex editor. It represents a new kind of Computer Assisted Instruction (CAI) system that integrates systematic teaching with actual practice, i.e., one which can keep the user under tutorial supervision while allowing him to try out what he learns on the system he is learning about. NLS-SCHOLAR can also be used as an on-line help system outside the tutorial environment, in the course of a user's actual work. This capability of combining on-line assistance with training is an extension of the traditional notion of CAI. The techniques used in NLS- SCHOLAR are general and can be applied to the teaching of a wide variety of computer related activities.

Some scientific inference tasks (including mass spectrum identification medical diagnosis, and math theory development have been successfully modelled as rule-directed search processes. These rule systems are designed quite differently from 'pure production systems'. By concentrating upon the design of one program (AM), we shall show how 13 kinds of design deviations arise from the level of sophistication of the task that the system is designed to perform, the inherent nature of the task, and the designer's view of the task. The limitations of AM suggest even more radical departures from traditional rule system architecture. All these modifications are then collected into a new, complicated set of constraints on the form of the data structures, the rules, the interpreter, and the distribution of knowledge between rules, and data structures. These new policies sacrifice uniformity in the interests of clarity, efficiency and power derivable from a thorough characterization of the task. Rule systems whose architectures conform to the new design principles will be more awkward for many tasks than would 'pure' systems. Nevertheless, the new architecture should be significantly more powerful and natural for building rule systems that do scientific discovery tasks.

In a study initiated to determine the biological effects of ELF electric and magnetic fields associated with a submarine communications system ELF-exposed male rhesus monkeys gained weight at a slightly faster rate than control males. In order to obtain sufficient data on the physiological effects of electromagnetic fields, a second ELF study was initiated. Whereas the first study was initiated with wild-caught young adult animals, the second study utilized colony-bred animals beginning at 30 days of age. The emphasis of the second study was to substantiate previous findings and determine the underlying mechanisms involved. As in the first study, 30 primates (male and female) were exposed to the ELF electric and magnetic fields, and 30 control animals received the same care and treatment, but were not exposed. This report deals with the development of the permanent teeth relative to ELF exposure and sex. A consistent trend noted was that the teeth of female animals erupted at a slightly earlier age than males. However, no significant differences due to ELF exposure or sex were detected. (Author)

A variable capacity centrifugal pump capable of directly varying capacity, or output, in response to existing back pressure. The pump comprises a axially movable shroud having female grooves in fluid tight communication with male impeller vanes. The shroud has a top faces surface in fluid communication with a control cavity which in turn is in fluid communication with pump back pressure. Patents. (RH), Supersedes PAT-APPL-159 490-88.

This report analyzes the effectiveness of applying the Quick Response Freight Manual (QRFM) to model freight, transportation. Typically freight transportation is modeled indirectly or as an after-thought. Increasing freight, volumes, coupled with cost-saving strategies such as just-in-time delivery systems, require that transportation, policymakers analyze infrastructure needs and make investment decisions that explicitly include freight volumes as, a component. This paper contains a case study using a travel model for a medium-sized urban area and the QRFM, trip-generation and distribution methodology to provide a framework for freight planning that can be used to, improve resource-allocation decisions