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Energy Systems and Population Health

Description: It is well-documented that energy and energy systems have a central role in social and economic development and human welfare at all scales, from household and community to regional and national (41). Among its various welfare effects, energy is closely linked with people s health. Some of the effects of energy on health and welfare are direct. With abundant energy, more food or more frequent meals can be prepared; food can be refrigerated, increasing the types of food items that are consumed and reducing food contamination; water pumps can provide more water and eliminate the need for water storage leading to contamination or increased exposure to disease vectors such as mosquitoes or snails; water can be disinfected by boiling or using other technologies such as radiation. Other effects of energy on public health are mediated through more proximal determinants of health and disease. Abundant energy can lead to increased irrigation, agricultural productivity, and access to food and nutrition; access to energy can also increase small-scale income generation such as processing of agricultural commodities (e.g., producing refined oil from oil seeds, roasting coffee, drying and preserving fruits and meats) and production of crafts; ability to control lighting and heating allows education or economic activities to be shielded from daily or seasonal environmental constraints such as light, temperature, rainfall, or wind; time and other economic resources spent on collecting and/or transporting fuels can be used for other household needs if access to energy is facilitated; energy availability for transportation increases access to health and education facilities and allow increased economic activity by facilitating the transportation of goods and services to and from markets; energy for telecommunication technology (radio, television, telephone, or internet) provides increased access to information useful for health, education, or economic purposes; provision of energy to rural and urban health ...
Date: April 12, 2004
Creator: Ezzati, Majid; Bailis, Rob; Kammen, Daniel M.; Holloway, Tracey; Price, Lynn; Cifuentes, Luis A. et al.
Partner: UNT Libraries Government Documents Department

EpiPOD : community vaccination and dispensing model user's guide.

Description: EpiPOD is a modeling system that enables local, regional, and county health departments to evaluate and refine their plans for mass distribution of antiviral and antibiotic medications and vaccines. An intuitive interface requires users to input as few or as many plan specifics as are available in order to simulate a mass treatment campaign. Behind the input interface, a system dynamics model simulates pharmaceutical supply logistics, hospital and first-responder personnel treatment, population arrival dynamics and treatment, and disease spread. When the simulation is complete, users have estimates of the number of illnesses in the population at large, the number of ill persons seeking treatment, and queuing and delays within the mass treatment system--all metrics by which the plan can be judged.
Date: January 9, 2009
Creator: Berry, M.; Samsa, M.; Walsh, D. & Sciences, Decision and Information
Partner: UNT Libraries Government Documents Department

FEASIBILITY OF THE AEROSOL-TO-LIQUID PARTICLE EXTRACTION SYSTEM (ALPES) FOR COLLECTION OF VIABLE FRANCISELLA SP.

Description: Several Biowatch monitoring sites in the Houston area have tested positive for Francisella tularensis and there is a need to determine whether natural occurring Francisella-related microorganism(s) may be responsible for these observed positive reactions. The collection, culturing and characterization of Francisella-related natural microorganisms will provide the knowledge base to improve the future selectivity of Biowatch monitoring for Francisella. The aerosol-to-liquid particle extraction system (ALPES) is a high-efficiency, dual mechanism collection system that utilizes a liquid collection medium for capture of airborne microorganisms. Since the viability of microorganisms is preserved better in liquid medium than on air filters, this project was undertaken to determine whether Francisella philomiragia and Francisella tularensis LVS maintain acceptable viability in the continuous liquid recirculation, high direct current voltage and residual ozone concentrations which occur during ALPES operation. Throughout a series of preliminary trial runs with representative gram-negative and gram-positive microorganisms, several design modifications and improvements to the ALPES optimized liquid handling, electrical stability, sampling and overall performance for biological sampling. Initial testing with Francisella philomiragia showed viability was preserved better in PBS buffer than HBSS buffer. Trial runs at starting cell concentrations of 1.8 x 10{sup 6} and 2.5 x 10{sup 4} CFU/L showed less than a 1-log decrease in viability for F. philomiragia after 24 h in the ALPES. Francisella tularensis LVS (live vaccine strain) was used as a surrogate for virulent F. tularensis in ALPES trial runs conducted at starting cell concentrations of 10{sup 4}, 10{sup 5} and 10{sup 6} CFU/L. F. tularensis LVS was slow-growing and required highly selective growth media to prevent overgrowth by collected airborne microorganisms. In addition, one ALPES unit intake was HEPA filtered during the final trial runs with F. tularensis LVS to further reduce the levels of microbial background. Results from trials with F. tularensis LVS showed about ...
Date: August 7, 2006
Creator: Heitkamp, M
Partner: UNT Libraries Government Documents Department

Modeling the effects of prior infection on vaccine efficacy

Description: We performed computer simulations to study the effects of prior infection on vaccine efficacy. We injected three antigens sequentially. The first antigen, designated the prior, represented a prior infection or vaccination. The second antigen, the vaccine, represented a single component of the trivalent influenza vaccine. The third antigen, the epidemic, represented challenge by an epidemic strain. For a fixed vaccine to epidemic strain cross-reactivities to the vaccine and to the epidemic strains. We found that, for many cross-reactivities, vaccination, when it had been preceded by a prior infection, provided more protection than vaccination alone. However, at some cross-reactivities, the prior infection reduced protection by clearing the vaccine before it had the chance to produce protective memory. The cross-reactivities between the prior, vaccine and epidemic strains played a major role in determining vaccine efficacy. This work has applications to understanding vaccination against viruses such as influenza that are continually mutating.
Date: November 1, 1997
Creator: Smith, D. J.; Forrest, S.; Ackley, D. H. & Perelson, A. S.
Partner: UNT Libraries Government Documents Department

Progress in rapid detection and identification of unknown human and agricultural pathogens

Description: The medical industry is driving pathogen detection technology from its present characteristics of $50/sample, 100 sample capability systems, with several day time responses, having several percent error rates in reported outcomes. The systems described above are capable of providing samples at < $5/test, managing several million samples, < 1-hour cycle times, (or just minutes in some cases) and < 0.1% error rates. Because of their importance to the medical and agricultural communities, all ''important'' pathogens will have detection kits available (within air transport times, anywhere in the world) by 2020, and the most well known pathogens will have kits available within a few years. Many are available now. Because of the importance of the food supply to modern nations, these technologies will be employed everywhere in this industry. For example, the United States imports 30 B tons of food a year, but inspects < 1%. Portable inspection systems will make it possible to test for dangerous pathogens in feed lots, food processing plants, markets, and points of use. Outbreaks of animal or plant disease will be immediately detectable using field instrumentation, and more complex samples can be sent to central testing laboratories where more sophisticated test systems will be available. Unusual pathogens either naturally or purposefully selected or developed, will require special attention because there is not a commercial economic driver for the development of detection systems and curative agents. Their development, and production for sufficient availability, will require significant investments by the world community. The strategy and costs for developing vaccines or curative drugs will be very expensive and will need special attention. However it is important that attention be directed to these problems because such attention has a strong deterrent effect on potential developers or users. The capacity to use the full information content contained in pathogen systems, ...
Date: August 13, 1999
Creator: Barnes, T; Holzrichter, J F & Milanovich, F P
Partner: UNT Libraries Government Documents Department

Advanced Algorithms for Rapidly Reconstructing Clandestine Releases of Biological Agents in Urban Areas

Description: As the United States plays a greater role in the 21st Century as global peacekeeper and international defender of human rights and democratic principles, there is an increasing likelihood that it will become the focus of acts of terrorism. Such acts of terrorism--sometimes described as ''asymmetric''--could involve the threat or use of weapons of mass destruction (WMD), particularly those considered unconventional, which include ones designed to release chemical or biological agents. In fact, biological agents are of great concern because, as noted by D.A. Henderson of the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore, MD, ''... with shortages of hospital space, vaccines, antibiotics, there would be chaos.'' (Williams, 2000). Unfortunately, potential aggressor nations, terrorist groups, and even individuals, can, for a modest cost and effort, develop covert capabilities for manufacturing, transporting, and offensively using biological weapons of mass destruction. Furthermore, there is evidence to indicate that terrorist increasingly are targeting civilian populations--in order to inflict indiscriminate casualties--as well as other more traditional targets such as symbolic buildings or organizations (see Tucker, 1999), which suggest that introducing rapid treatment after a biological event may be more practical than concentrating on prevention (see Siegrist, 1999), especially because sensors are unlikely to be placed in all major urban areas to detect even an atmospheric biological release. For these reasons, and because symptoms for the majority of those effected may not occur or be directly identified for several days, early identification of a covert undetected biological event (CUBE) will contribute to timely medical intervention, which can save many lives.
Date: February 25, 2000
Creator: Shinn, J.H.; Hall, C.H.; Neher, L.A.; Wilder, F.J.; Gouveia, D.W.; Layton, D.W. et al.
Partner: UNT Libraries Government Documents Department

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1988 Final Report.

Description: Bacterial kidney disease of salmonids is a very complex disease which appears to exploit a variety of pathogenic mechanisms. An understanding of these mechanisms is essential to the development of efficacious vaccines. It has become well established from the studies published .in this report and those of others that soluble antigens which are secreted by Renibacterium salmoninarum have toxigenic potential. If they are found to be responsible for mortality, the development of toxoid(s) could be paramount to the production of a vaccine. One must, however, be circumspect in producing a vaccine. A thorough knowledge, not only of the pathogen, but also of the immune system of the host is an absolute requirement. This becomes of particular importance when dealing with fish diseases, since the field of fish immunology is still within its infancy. This lack of knowledge is particularly felt when the induction of a prophylactic immune response concomitantly leads to pathological side effects which may be as destructive as the original infection. Indeed, it appears that some aspects of BKD may be due to the induction of hypersensitivity reactions. If such immunopathologies are expressed, it is prudent to thoroughly evaluate the nature of the immunoprophylaxis to insure that these harmful sequelae do not occur. Evaluation of a variety of antigens, adjuvants, immune responses, and survival data leads us to recommend that attempts at prophylaxis against BKD should center upon the elicitation of cellular immunity utilizing preparations of Mycobacterium chelonii. The choice of this species of mycobacteria was made because of its effectiveness, ease of maintenance and production, and the lack of need for its propagation within containment facilities. These assets are important to consider if large scale vaccine production is to be profitable. As can be seen from the data provided, M. chelonii alone is capable of producing prophylaxis ...
Date: August 1, 1989
Creator: Kaattari, Stephen L.
Partner: UNT Libraries Government Documents Department

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1984 Annual Report.

Description: The data presented here demonstrate that there is some variability to the antigenic structure of KDB. Although gel filtration of all antigenic preparations revealed a wide range of sizes for antigens, resolution on a denaturing gel revealed relatively few protein bands and immunological assays revealed the same (3) low number of antigens. It is of particular interest that there seems to be a protein of 60 kd in all preparations, but that there are not larger individual molecular species. This, in turn indicates that the larger molecular weight species detected in gel filtration are most likely aggregates or membrane fragments composed of a lower molecular weight subunit. Use of ultrafiltration of KDM-2 medium appears to be successful in eliminating contamination of high molecular weight material found in KDM-2. There appears to be no alteration in the number of soluble antigens produced by growth in either medium, nor in the number of proteins, as detected by SDS-PAGE. However, soluble antigens isolated from UF-KDM-2 does appear to have greater heterogeneity in their isoelectric focusing (IEF) patterns than those from UF-KDM-2. Also, although there does appear to be an extended lag period in KDB growth on UF-KDM-2, there is no alteration in final O.D. or wet weight of cells. Thus, it appears that UF-KDM-2 may be an alternate medium for those wishing to isolate purified bacterial proteins or antigens. ELISA assays have been developed for the detection of soluble KDB antigens. This system is currently being developed as a sensitive measure of the presence of soluble antigen in serum and tissues of fish. Such a sensitive assay may also allow for the detection of KD+ spawners by the testing of ovarian fluid or serum. ELISA assays have also been developed to detect antibodies to soluble and cellular antigens of KDB. These systems have ...
Date: June 1, 1985
Creator: Kaattari, Stephen L.
Partner: UNT Libraries Government Documents Department

Biochemical and biophysical characterization of the major outer surface protein, OSP-A from North American and European isolates of Borrelia burgdorferi

Description: Lyme borreliosis, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in North America and Western Europe. As the major delayed immune response in humans, a better understanding of the major outer surface lipoproteins OspA and OspB are of much interest. These proteins have been shown to exhibit three distinct phylogenetic genotypes based on their DNA sequences. This paper describes the cloning of genomic DNA for each variant and amplification of PCR. DNA sequence data was used to derive computer driven phylogenetic analysis and deduced amino acid sequences. Overproduction of variant OspAs was carried out in E. coli using a T7-based expression system. Circular dichroism and fluorescence studies was carried out on the recombinant B31 PspA yielding evidence supporting a B31 protein containing 11% alpha-helix, 34% antiparallel beta-sheet, 12% parallel beta sheet.
Date: December 31, 1995
Creator: McGrath, B.C.; Dunn, J.J.; France, L.L.; Jaing, W.; Polin, D.; Gorgone, G. et al.
Partner: UNT Libraries Government Documents Department

Agricultural pathogen decontamination technology-reducing the threat of infectious agent spread.

Description: Outbreaks of infectious agricultural diseases, whether natural occurring or introduced intentionally, could have catastrophic impacts on the U.S. economy. Examples of such agricultural pathogens include foot and mouth disease (FMD), avian influenza (AI), citrus canker, wheat and soy rust, etc. Current approaches to mitigate the spread of agricultural pathogens include quarantine, development of vaccines for animal diseases, and development of pathogen resistant crop strains in the case of plant diseases. None of these approaches is rapid, and none address the potential persistence of the pathogen in the environment, which could lead to further spread of the agent and damage after quarantine is lifted. Pathogen spread in agricultural environments commonly occurs via transfer on agricultural equipment (transportation trailers, tractors, trucks, combines, etc.), having components made from a broad range of materials (galvanized and painted steel, rubber tires, glass and Plexiglas shields, etc), and under conditions of heavy organic load (mud, soil, feces, litter, etc). A key element of stemming the spread of an outbreak is to ensure complete inactivation of the pathogens in the agricultural environment and on the equipment used in those environments. Through the combination of enhanced agricultural pathogen decontamination chemistry and a validated inactivation verification methodology, important technologies for incorporation as components of a robust response capability will be enabled. Because of the potentially devastating economic impact that could result from the spread of infectious agricultural diseases, the proposed capability components will promote critical infrastructure protection and greater border and food supply security. We investigated and developed agricultural pathogen decontamination technologies to reduce the threat of infectious-agent spread, and thus enhance agricultural biosecurity. Specifically, enhanced detergency versions of the patented Sandia decontamination chemistry were developed and tested against a few surrogate pathogens under conditions of relatively heavy organic load. Tests were conducted on surfaces commonly found in agricultural ...
Date: October 1, 2005
Creator: Betty, Rita G.; Bieker, Jill Marie & Tucker, Mark David
Partner: UNT Libraries Government Documents Department

Modeling the Effects of Updating the Influenza Vaccine on the Efficacy of Repeated Vaccination

Description: The accumulated wisdom is to update the vaccine strain to the expected epidemic strain only when there is at least a 4-fold difference [measured by the hemagglutination inhibition (HI) assay] between the current vaccine strain and the expected epidemic strain. In this study we investigate the effect, on repeat vaccines, of updating the vaccine when there is a less than 4-fold difference. Methods: Using a computer model of the immune response to repeated vaccination, we simulated updating the vaccine on a 2-fold difference and compared this to not updating the vaccine, in each case predicting the vaccine efficacy in first-time and repeat vaccines for a variety of possible epidemic strains. Results: Updating the vaccine strain on a 2-fold difference resulted in increased vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged. Conclusions: These results suggest that updating the vaccine strain on a 2-fold difference between the existing vaccine strain and the expected epidemic strain will increase vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged.
Date: November 1, 2000
Creator: Smith, Derek J.; Lapedes, Alan S.; Forrest, Stephanie; deJong, Jan C.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M. et al.
Partner: UNT Libraries Government Documents Department

The Food and Drug Administration Safety and Innovation Act (P.L. 112-144)

Description: This report provides a brief policy background narrative and an overview of provisions for each title of the Food and Drug Administration Safety and Innovation Act (FDASIA), P.L. 112-144. The legislation amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to expand the authority of the Food and Drug Administration (FDA) in performing its human drug, biological product, and medical device responsibilities.
Date: August 21, 2012
Creator: Thaul, Susan; Bagalman, Erin; Corby-Edwards, Amalia K.; Glassgold, Judith M.; Johnson, Judith A.; Lister, Sarah A. et al.
Partner: UNT Libraries Government Documents Department

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1985 Annual Report.

Description: Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's second year was to chemically modify the major antigens of Renibacteirium salmoninarum, immunize coho salmon (Oncorhynchus kisutch), and to test the immunogenicity of the preparations used. Immunogenicity of the antigenic material was tested by (1) admixture experiments, using whole KD cells with muramyl dipepetide, Vibrio anguillarum extract, E. coli lipopolysaccharide, or Mycobacterium tuberculosis in Freund's complete adjuvant. In addition to these goals a number of important techniques have been developed in order to facilitate the production of the vaccine. These procedures include: (1) the use of the soluble antigen for diagnosis in the ELISA and Western blot analysis, (2) detection of salmonid anti-KD antibodies by an ELISA technique, (3) detection of cellular immune responses to the soluble antigen, and (4) development of immersion challenge procedures for bacterial kidney disease (BKD).
Date: June 1, 1986
Creator: Kaattari, Stephen L.
Partner: UNT Libraries Government Documents Department

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1986 Annual Report.

Description: Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon of the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon of Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem,and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's third year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various chemical conjugates of Renibacterium salmoninarum cells and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (cellular proliferation), and the kinetics of mortality after Lethal injections of the bacterium. An important facet of this research is the identification and isolation of virulence factors. These studies are not only important to the dissection of the mechanism of pathogenesis of bacterial kidney disease, but the purification of such a factor(s) will insure the production of a more potent vaccine. The studies completed this year have: (1) identified antigenic material which protect; (2) identified antigenic material which can exacerbate the disease; (3) identified a possibly major mechanism of pathogenesis via the interference with antibody; (4) the general ability to produce delineated a western blot technique for identification of infected fish; (5) described the use of monoclonal antibodies ...
Date: June 1, 1987
Creator: Kaattari, Stephen L.
Partner: UNT Libraries Government Documents Department

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1987 Annual Report.

Description: Bacterial kidney disease (BKD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's fourth year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various--chemical conjugates of Renibacterium salmoninarum cell and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (chemiluminescence), and the kinetics of mortality after lethal injections of the bacteria. The studies completed this year have: (1) identified immunization procedures which enhance the induction of high levels of antibody; (2) identified functionally distinct serum antibodies which may possess different abilities to protect salmon against BKD; (3) begun the isolation and characterization of anti-R. salmoninarum antibodies which may correlate with varying degrees of protection; (4) identified chemiluminescence as a potential method for assessing cellular immunity to bacterial kidney disease; and (5) characterized two monoclonal antibodies to R. salmoninarum which will be of benefit in the diagnosis of this disease.
Date: June 1, 1988
Creator: Kaattari, Stephen
Partner: UNT Libraries Government Documents Department

Research on Captive Broodstock Programs for Pacific Salmon, 2001-2002 Annual Report.

Description: The efficacy of captive broodstock programs depends on high in-culture survival and the fitness of cultured salmon after release, either as adults or juveniles. Continuing captive broodstock research designed to improve technology is being conducted to cover all major life history stages of Pacific salmon. The following summarizes some of the work performed and results from the FY 2001 performance period: (1) The incidence of male maturation of age-1 chinook salmon was significantly reduced by reducing growth in the first year of rearing. (2) Experimentally manipulated growth rates of captively-reared coho salmon had significant effects on female maturation rate, egg size, and fecundity, and the effects were stage-specific (i.e., pre-smolt vs. post-smolt). (3) A combination of Renogen and MT239 vaccination of yearling chinook salmon given an acute R. salmoninarum challenge had a significantly longer survival time than the mock-vaccinated group. The survival time was marginally higher than was seen in acutely challenged fish vaccinated with either Renogen or MT239 alone and suggests that a combination vaccine of Renogen and MT239 may be useful as both a prophylactic and therapeutic agent against BKD. (4) Full-sib (inbred) groups of chinook salmon have thus far exhibited lower ocean survival than half-sib and non-related groups. Effects of inbreeding on fluctuating asymmetry did not follow expected patterns. (5) Sockeye salmon were exposed to specific odorants at either the alevin/emergent fry stage or the smolt stage to determine the relative importance of odorant exposure during key developmental periods and the importance of exposure duration. (6) Experimental studies to determine the effects of exercise conditioning on steelhead reproductive behavior and the effects of male body size on chinook salmon fertilization success during natural spawning were completed.
Date: August 1, 2002
Creator: Berejikian, Barry; Tezak, E. & Endicott, Rick
Partner: UNT Libraries Government Documents Department

Research on Captive Broodstock Programs for Pacific Salmon; Assessment of Captive Broodstock Technologies, Annual Report 2002-2003.

Description: The success of captive broodstock programs depends on high in-culture survival, appropriate development of the reproductive system, and the behavior and survival of cultured salmon after release, either as adults or juveniles. Continuing captive broodstock research designed to improve technology is being conducted to cover all major life history stages of Pacific salmon. Current velocity in rearing vessels had little if any effect on reproductive behavior of captively reared steelhead. However, males and females reared in high velocity vessels participated a greater number of spawning events than siblings reared in low velocity tanks. Observations of nesting females and associated males in a natural stream (Hamma Hamma River) were consistent with those observed in a controlled spawning channel. DNA pedigree analyses did not reveal significant differences in the numbers of fry produced by steelhead reared in high and low velocity vessels. To determine the critical period(s) for imprinting for sockeye salmon, juvenile salmon are being exposed to known odorants at key developmental stages. Subsequently they will be tested for development of long-term memories of these odorants. In 2002-2003, the efficacy of EOG analysis for assessing imprinting was demonstrated and will be applied in these and other behavioral and molecular tools in the current work plan. Results of these experiments will be important to determine the critical periods for imprinting for the offspring of captively-reared fish destined for release into natal rivers or lakes. By early August, the oocytes of all of Rapid River Hatchery chinook salmon females returning from the ocean had advanced to the tertiary yolk globule stage; whereas, only some of the captively reared Lemhi River females sampled had advanced to this stage, and the degree of advancement was not dependent on rearing temperature. The mean spawning time of captive Lemhi River females was 3-4 weeks after that of ...
Date: January 1, 2004
Creator: Berejikian, Barry
Partner: UNT Libraries Government Documents Department

Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

Description: We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.
Date: January 1, 2008
Creator: Hraber, Peter; Giorgi, Elena E; Keele, Brandon; Li, Hui & Learn, Gerald
Partner: UNT Libraries Government Documents Department

Evolving T-cell vaccine strategies for HIV, the virus with a thousand faces

Description: HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effect (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy ...
Date: January 1, 2009
Creator: Korber, Bette
Partner: UNT Libraries Government Documents Department

Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

Description: An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T -cell-based HIV -1 vaccines.
Date: January 1, 2009
Creator: Korber, Bette; Fischer, William & Wallstrom, Timothy
Partner: UNT Libraries Government Documents Department

The race between infection and immunity - how do pathogens set the pace?

Description: Infection is often referred to as a race between pathogen and immune response. This metaphor suggests that slower growing pathogens should be more easily controlled. However, a growing body ofevidence shows that many chronic infections are caused by failure to control slow growing pathogens. The slow growth of pathogens appears to directly affect the kinetics of the immune response. Compared with the response to fast growing pathogens, the T cell response to slow pathogens is delayed in its initiation, lymphocyte expansion is slow and the response often fails to clear the pathogen, leading to chronic infection. Understanding the 'rules ofthe race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections.
Date: January 1, 2009
Creator: Ribiero, Ruy M
Partner: UNT Libraries Government Documents Department

Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

Description: The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in research laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been shown to regulate expression of virulence factor genes, including genes encoding type III secretion, via quorum sensing. The Y. pestis genome encodes several cell-cell signaling pathways and the interaction of at least three of these are thought to be involved in one or more modes of host invasion. Furthermore, Y. pestis gene expression array studies carried out at LLNL have established a correlation between expression of known virulence factors and genes involved in processing of the AI-2 quorum sensing signal. This was a basic research project that was intended to provide new insights into bacterial intercellular communication and how it ...
Date: March 29, 2010
Creator: Segelke, B; Hok, S; Lao, V; Corzett, M & Garcia, E
Partner: UNT Libraries Government Documents Department