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Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen.
Breaking the state of immunological unresponsiveness of tumor-bearing individuals to cancer is a prerequisite for active or passive tumor-specific immunotherapy. To study this problem the immunogenic MHC class I antigen, K216 was transfected into a progressor tumor. The transfected tumors were regularly rejected by normal mice but grew progressively in mice bearing nontransfected tumors. In addition, transgenic mice were derived to obtain normal cells and tissues expressing the same K216 gene product. Normal mice rejected K216-positive normal or malignant tissue grafts and generated K216-specific CTL in vitro and in vivo in response to these challenges. In contrast, mice bearing nontransfected tumors, though rejecting K216-positive nonmalignant tissue grafts, did not reject K216-positive tumors nor generate K216-specific CTL in response to K216-positive tumor cells. Mice bearing K216-positive tumors also rejected the nonmalignant K216-positive tissue grafts, but this in vivo response failed to lead to rejection of the simultaneously present tumor graft expressing the same antigen; in fact, immunity had no measurable effect whatsoever on tumor size or incidence and caused no selection for antigen loss variants. Taken together, the present findings suggest that transfer of expression of a target antigen into nonmalignant cells provides a way for obtaining effective stimulation of antigen-specific CTL in tumor-bearing mice, but that additional manipulations will be required to cause immunological rejection of established tumors
APU diaphragm testing
The Auxiliary Power Unit (APU) fuel (hydrazine) tanks were removed from the Columbia Shuttle during major modification of the vehicle, because of long-term hydrazine compatibility concerns. The three tanks had been in service for 11 years. As part of an effort to determine whether the useful life of the fuel tanks can be extended, examination of the ethylene propylene rubber (EPR) diaphragm and the metal casing from one of the APU tanks was required. NASA Johnson Space Center Propulsion and Power Division requested the NASA Johnson Space Center White Sands Test Facility to examine the EPR diaphragm for signs of degradation that might limit the life of its function in the APU tank and to examine the metal casing for signs of surface corrosion. No appreciable degradation of the EPR diaphragm was noted. A decrease in the tensile properties was found, but tensile failure is considered unlikely because the metal casing constrains the diaphragm, preventing it from elongating more than a few percent. The titanium casing showed no evidence of surface corrosion
Operative strategy for fistula-in-ano without division of the anal sphincter
We would like to thank Mr ER MacDonald for his contribution in data collection during the early years of the study. The material in this paper was presented as a poster at the annual meeting of the American Society of Colon and Rectal Surgeons held in Vancouver, Canada, May 2011.Peer reviewedPublisher PD
Barriers to Curriculum Technology Integration in Education
Many barriers have been placed in the path of school curriculum reform involving technology
Evaluating Mood Changes in Response to Anthropogenic Noise with a Response-Slowing Task in Three Species of Zoo-housed Primates
In the zoo environment, anthropogenic noise is common as sound levels fluctuate due to visitors, construction, habitat design, and special events. In this study, changes in the mood of three species of zoo-housed primates in response to a loud annual event were evaluated with the response-slowing paradigm. In this paradigm, animals experiencing anxiety slow responses on simple cognitive tasks when emotional content is displayed. Following a previously validated approach, we measured latencies to touch potentially threatening (conspecific faces with directed gaze) and non-threatening (conspecific faces with averted gaze) images overlaid on a grey square, relative to neutral control images (grey squares only) on a touchscreen. In Experiment 1, four Japanese macaques (Macaca fuscata) were tested in two conditions: during a baseline (non-stressful) period and opportunistically during three days during which loud jets frequently flew overhead. Results indicated a significant effect of condition, with an increase in latency to touch images of conspecific faces relative to control images during the days of the loud event. In Experiment 2, chimpanzees (Pan troglodytes, n = 4) and western lowland gorillas (Gorilla gorilla gorilla, n = 2) were tested during the same loud event following a similar methodology. The results revealed subtle changes across conditions; however, this was likely driven by the apes increasing their response speed to face stimuli relative to control stimuli over time (habituation). These findings suggest that the macaques, but not the apes, underwent detectable affective changes during the loud event. With additional development, this relatively simple paradigm may be an effective and feasible way to evaluate real-time changes in the mood of zoo-housed animals
A model for measuring the health burden of classic congenital adrenal hyperplasia in adults
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Aim: Patients with classic Congenital Adrenal Hyperplasia (CAH) have poor health
outcomes. In the absence of a comprehensive observational study, this manuscript provides a
model to estimate the lifetime disease burden of adults with classic CAH.
Methods: The model, built in Excel, comprises sub-domains addressing the health
consequences of CAH, and synthesises evidence from clinical and epidemiological studies on
health outcomes.
Results: The model estimates that adults with classic CAH will implement āsick day rulesā
(doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their
lifetime, and attend hospital for adrenal crisis on 11 occasions. In a population of 1,000, over
200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7
years of life. CAH patients may also suffer from excess CVD events. Treatment with
glucocorticoids almost doubles the risk of bone fractures in CAH patients compared to the
general population, leading on average to an additional 0.8 fractures per CAH patient over
their lifetime.
Conclusions: The disease burden model highlights gaps in evidence, particularly regarding
intensity of care and adrenal crisis, and the relationship between control of CAH and risks of
CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact
of new clinical pathways and therapeutic interventions in terms of clinical events and cost.Funded by: European Commission under the Framework 7 programme. Grant Number: HEALTH-F5-2011-281654Diurnal Limited (UK
Specific Image Characteristics Influence Attitudes about Chimpanzee Conservation and Use as Pets
Chimpanzees are endangered in their native Africa but in the United States, they are housed not only in zoos and research centers but owned privately as pets and performers. In 2008, survey data revealed that the public is less likely to think that chimpanzees are endangered compared to other great apes, and that this is likely the result of media misportrayals in movies, television and advertisements. Here, we use an experimental survey paradigm with composite images of chimpanzees to determine the effects of specific image characteristics. We found that those viewing a photograph of a chimpanzee with a human standing nearby were 35.5% more likely to consider wild populations to be stable/healthy compared to those seeing the exact same picture without a human. Likewise, the presence of a human in the photograph increases the likelihood that they consider chimpanzees as appealing as a pet. We also found that respondents seeing images in which chimpanzees are shown in typically human settings (such as an office space) were more likely to perceive wild populations as being stable and healthy compared to those seeing chimpanzees in other contexts. These findings shed light on the way that media portrayals of chimpanzees influence public attitudes about this important and endangered species
Comparison of performance-based measures among native Japanese, Japanese-Americans in Hawaii and Caucasian women in the United States, ages 65 years and over: a cross-sectional study
BACKGROUND: Japanese (both in Japan and Hawaii) have a lower incidence of falls and of hip fracture than North American and European Caucasians, but the reasons for these differences are not clear. SUBJECTS AND METHODS: A cross-sectional study. We compared neuromuscular risk factors for falls using performance-based measures (chair stand time, usual and rapid walking speed, and grip strength) among 163 Japanese women in Japan, 681 Japanese-American women in Hawaii and 9403 Caucasian women in the United States aged 65 years and over. RESULTS: After adjusting for age, the Caucasian women required about 40% more time to complete 5 chair stands than either group of Japanese. Walking speed was about 10% slower among Caucasians than native Japanese, whereas Japanese-American women in Hawaii walked about 11% faster than native Japanese. Grip strength was greatest in Japan, which may reflect the rural farming district that this sample was drawn from. Additional adjustment for height, weight or body mass index increased the adjusted means of chair stand time and grip strength among Japanese, but the differences remained significant. CONCLUSIONS: Both native Japanese and Japanese-American women in Hawaii performed better than Caucasians on chair stand time and walking speed tests, and native Japanese had greater grip strength than Japanese in Hawaii and Caucasians. The biological implications of these differences in performance are uncertain, but may be useful in planning future comparisons between populations
Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus
Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naĆÆve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. Ā© 2010 Bhardwaj et al
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