A Monte Carlo Model for Interrogation of Thick Cargos for Clandestine Fissionable Materials; Tests with 14-MeV Neutrons

A Monte Carlo model has been developed for interrogation of fissionable material embedded in thick cargos when high-energy {beta}-delayed {gamma} rays are detected following neutron-induced fission. The model includes the principal structural components of the laboratory, the neutron source and collimator assembly in which it resides, the assembly that represents cargo of given characteristics, a target of highly-enriched uranium (HEU) and large external plastic scintillators for photon detection. The ability of this model to reproduce experimental measurements was tested by comparing simulations with measurements of the number of induced fissions and the number of detected photons when the HUE target was irradiated with 14.25-MeV neutrons in the absence of any cargo and while embedded in assemblies of plywood and iron pipes. The simulations agreed with experimental measurements within a factor of about 2 for irradiation of the bare target and when the areal density of intervening cargo was 33 g cm{sup -2} (wood) and 61 g cm{sup -2} (steel pipes). This suggests that the model can permit exploration of a large range in parameter space with reasonable fidelity

Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis

Cytolysis mediated by complement or cytolytic lymphocytes results in the formation of morphology similar lesions in the target membrane. These lesions, formed by the polymerization of C9 or perforin respectively, contribute the major killing action by causing osmotic lysis of the target cell. Following the suggestion of Mayer that the mechanisms of humoral and cell-mediated cytotoxicity might be related, studies into the morphology of the membrane lesions formed, and the proteins responsible for causing the lesions, have shown several similarities. While the lesion caused by natural and T-killer cells is a little larger than that caused by complement, its overall shape is similar and in both cases the cylindrical pore is formed by polymerization of a monomeric subunit, C9 (relative molecular mass, Mr = 71,000) for complement, and perforin (Mr = 66,000) for cell-mediated cytotoxicity. C9 has an absolute requirement for a receptor in the target membrane formed by the earlier membrane attack complex components, C5b, C6, C7 and C8 (ref. 8). For perforin, polymerization in a target membrane requires no receptor, specificity being derived from the specific recognition between killer and target cell. Both proteins can be made to polymerize in vitro by the addition of divalent cations (Zn2+ for C9 (ref. 16) and Ca2+ for perforin) and the resultant complexes closely resemble their physiological counterparts. Antibodies raised against lymphocyte-killed targets have also been shown to cross-react with complement proteins, but the antigenically related proteins were not determined in these studies. We show here using purified proteins that perforin, C9 and complexes involving C7 and C8 share a common antigenic determinant which is probably involved in polymerization

The inflammatory effects of TNF-α and complement component 3 on coagulation

CITATION: Page, M. J., Bester, J. & Pretorius, E. 2018. The inflammatory effects of TNF-α and complement component 3 on coagulation. Scientific Reports, 8:1812, doi:10.1038/s41598-018-20220-8.The original publication is available at http://www.nature.comPublication of this article was funded by the Stellenbosch University Open Access Fund.Tissue necrosis factor-α (TNF-α) and complement component 3 (C3) are two well-known pro-inflammatory molecules. When TNF-α is upregulated, it contributes to changes in coagulation and causes C3 induction. They both interact with receptors on platelets and erythrocytes (RBCs). Here, we look at the individual effects of C3 and TNF-α, by adding low levels of the molecules to whole blood and platelet poor plasma. We used thromboelastography, wide-field microscopy and scanning electron microscopy to study blood clot formation, as well as structural changes to RBCs and platelets. Clot formation was significantly different from the naïve sample for both the molecules. Furthermore, TNF-α exposure to whole blood resulted in platelet clumping and activation and we noted spontaneous plasma protein dense matted deposits. C3 exposure did not cause platelet aggregation, and only slight pseudopodia formation was noted. Therefore, although C3 presence has an important function to cause TNF-α release, it does not necessarily by itself cause platelet activation or RBC damage at these low concentrations. We conclude by suggesting that our laboratory results can be translated into clinical practice by incorporating C3 and TNF-α measurements into broad spectrum analysis assays, like multiplex technology, as a step closer to a patient-orientated, precision medicine approach.https://www.nature.com/articles/s41598-018-20220-8Publisher's versio