Radiation hardening of components and systems for nuclear rocket vehicle applications

The results of the analysis of the S-2 and S-4B components, although incomplete, indicate that many Saturn 5 components and subsystems, e.g., pumps, valves, etc., can be radiation hardened to meet NRV requirements by material substitution and minor design modifications. Results of these analyses include (1) recommended radiation tolerance limits for over 100 material applications; (2) design data which describes the components of each system; (3) presentation of radiation hardening examples of systems; and (4) designing radiation effects tests to supply data for selecting materials

A preliminary design study of a microparticle accelerator final report, 30 jan. - 13 apr. 1964

Design study for 2MV microparticle accelerato

Kinetics Of Egg Production And Egg Excretion By Schistosoma Mansoni And S. Japonicum In Mice Infected With A Single Pair Of Worms

Individual male and female schistosomes approximately three weeks of age were implanted into the portal venous system of C57Bl/6 mice to produce infections with a single pair of Schistosoma mansoni or S. japonicum. Mice were killed between seven and 53 weeks after infection. Worm fecundity was measured by counting eggs accumulating in the tissues and eggs passed in the feces. Schistosoma mansoni worm pairs laid approximately 350 eggs per day with no change in the apparent rate of egg laying between eight and 52 weeks after infection and approximately one-third of the eggs were passed in the feces. Schistosoma japonicum worm pairs laid approximately 2,200 eggs per day initially and this decreased to 1,000 eggs per day by the end of the experiment, with one-third to one-half of the eggs being passed in the feces. Then was marked variability in the fecundity of individual worm pairs, but the number of eggs passed in the feces of individual mice correlated well with the number of eggs in the intestines at all time points in S. mansoni-infected mice and at the seventh and tenth week of S. japonicum infection

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Persistence Of Eggs And Hepatic-Fibrosis After Treatment Of Schistosoma Mansoni-Infected Mice

In 1971 we estimated that Schistosoma mansoni eggs in the tissues of mice were destroyed with an approximate half-life of four weeks. Our present results of five experiments suggest that egg destruction is not as rapid, and no significant destruction of eggs was detected for up to 26 weeks after treatment. However, in these experiments, a mean of 60% of the eggs in intestinal tissues were found in the feces at the time of treatment. In previously reported experiments, only 15% of gut eggs were passed in the feces. We now believe that underestimation of the number of eggs passed in the feces led to an overestimation of the number of eggs destroyed in the tissues. We analyzed liver eggs separately because eggs lost from this site are unaffected by eggs passed in the feces. No significant decrease in liver eggs occurred in the present experiments, but reanalysis of previously published data showed significant egg destruction in the liver in several experiments, although at a much slower rate than previously estimated. However, inspection of the data in the previously published and present experiments does not show a convincing difference in the number of eggs in the liver after treatment. The persistence of egg shells is probably not important in the pathogenesis of disease, but is of concern in calculating worm fecundity. Hepatic collagen levels increased markedly two weeks after treatment and subsequently decreased significantly in some, but not all, experiments

Natural History Of Schistosoma Mansoni Infection In Mice: Egg Production, Egg Passage In The Feces, And Contribution Of Host And Parasite Death To Changes In Worm Numbers

Mice, C57B1/6N (B6) and BALB/cAnN (BALB), infected with Schistosoma mansoni were examined 8-26 weeks postinfection (PI) to estimate the fecundity of the worms and the contribution of death of worms and the death of heavily infected mice to the decrease in worm numbers in chronic infections. Portal worms were recovered by perfusion and the lungs were examined for parasites shunted from the portal circulation. Animals that died were more heavily infected than those that survived. Between eight and 12 weeks PI, this loss of worms resulted in a net decrease of approximately 19% of worm Fairs in surviving BALB mice, but of only 4% in B6 mice. Loss of portal worms to the lungs after the eighth week of infection was 9-13% of portal worms in BALB mice and 3-4% in B6 mice. The estimated rates of egg production by S. mansoni decreased slightly with time in both strains of mice. At 12 and 20 weeks PI, tissue eggs per worm pair and eggs passed in the feces per worm pair often decreased as the intensity of infection increased. We do not consider the loss of worms in the murine host relevant to most infections in humans because of the high intensity of infection relative to body size in mice and the high frequency of severe portal obstruction in murine infections

Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area

Background: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. Methods: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. Results: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). Conclusions: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment

Retnla (Relmα/Fizz1) Suppresses Helminth-Induced Th2-Type Immunity

Retnla (Resistin-like molecule alpha/FIZZ1) is induced during Th2 cytokine immune responses. However, the role of Retnla in Th2-type immunity is unknown. Here, using Retnla−/− mice and three distinct helminth models, we show that Retnla functions as a negative regulator of Th2 responses. Pulmonary granuloma formation induced by the eggs of the helminth parasite Schistosoma mansoni is dependent on IL-4 and IL-13 and associated with marked increases in Retnla expression. We found that both primary and secondary pulmonary granuloma formation were exacerbated in the absence of Retlna. The number of granuloma-associated eosinophils and serum IgE titers were also enhanced. Moreover, when chronically infected with S. mansoni cercariae, Retnla−/− mice displayed significant increases in granulomatous inflammation in the liver and the development of fibrosis and progression to hepatosplenic disease was markedly augmented. Finally, Retnla−/− mice infected with the gastrointestinal (GI) parasite Nippostrongylus brasiliensis had intensified lung pathology to migrating larvae, reduced fecundity, and accelerated expulsion of adult worms from the intestine, suggesting Th2 immunity was enhanced. When their immune responses were compared, helminth infected Retnla−/− mice developed stronger Th2 responses, which could be reversed by exogenous rRelmα treatment. Studies with several cytokine knockout mice showed that expression of Retnla was dependent on IL-4 and IL-13 and inhibited by IFN-γ, while tissue localization and cell isolation experiments indicated that eosinophils and epithelial cells were the primary producers of Retnla in the liver and lung, respectively. Thus, the Th2-inducible gene Retnla suppresses resistance to GI nematode infection, pulmonary granulomatous inflammation, and fibrosis by negatively regulating Th2-dependent responses