A D-D/D-T fusion reaction based neutron generator system for liver tumor BNCT

Boron-neutron capture therapy (BNCT) is an experimental radiation treatment modality used for highly malignant tumor treatments. Prior to irradiation with low energetic neutrons, a 10B compound is located selectively in the tumor cells. The effect of the treatment is based on the high LET radiation released in the {sup 10}B(n,{alpha}){sup 7}Li reaction with thermal neutrons. BNCT has been used experimentally for brain tumor and melanoma treatments. Lately applications of other severe tumor type treatments have been introduced. Results have shown that liver tumors can also be treated by BNCT. At Lawrence Berkeley National Laboratory, various compact neutron generators based on D-D or D-T fusion reactions are being developed. The earlier theoretical studies of the D-D or D-T fusion reaction based neutron generators have shown that the optimal moderator and reflector configuration for brain tumor BNCT can be created. In this work, the applicability of 2.5 MeV neutrons for liver tumor BNCT application was studied. The optimal neutron energy for external liver treatments is not known. Neutron beams of different energies (1eV < E < 100 keV) were simulated and the dose distribution in the liver was calculated with the MCNP simulation code. In order to obtain the optimal neutron energy spectrum with the D-D neutrons, various moderator designs were performed using MCNP simulations. In this article the neutron spectrum and the optimized beam shaping assembly for liver tumor treatments is presented

Experiments with planar inductive ion source meant for creation ofH+ Beams

In this article the effect of different engineering parameters of an rf-driven ion sources with external spiral antenna and quartz disk rf-window are studied. Paper consists of three main topics: The effect of source geometry on the operation gas pressure, the effect of source materials and magnetic confinement on extracted current density and ion species and the effect of different antenna geometries on the extracted current density. The operation gas pressure as a function of the plasma chamber diameter, was studied. This was done with three cylindrical plasma chambers with different inner diameters. The chamber materials were studied using two materials, aluminum and alumina (AlO{sub 2}). The removable 14 magnet multicusp confinement arrangement enabled us to compare the effects of the two wall materials with and without the magnetic confinement. Highest proton fraction of {approx} 8% at 2000 W of rf-power and at pressure of 1.3 Pa was measured using AlO{sub 2} plasma chamber and no multicusp confinement. For all the compared ion sources at 1000W of rf-power, source with multicusp confinement and AlO2 plasma chamber yields highest current density of 82.7 mA/cm{sup 2} at operation pressure of 4 Pa. From the same source highest measured current density of 143 mA/cm{sup 2} at 1.3 Pa and 2200W of rf-power was achieved. Multicusp confinement increased the maximum extracted current up to factor of two. Plasma production with different antenna geometries was also studied. Antenna tests were performed using same source geometry as in source material study with AlO{sub 2} plasma chamber and multicusp confinement. The highest current density was achieved with 4.5 loop solenoid antenna with 6 cm diameter. Slightly lower current density with lower pressure was achieved using tightly wound 3 loop spiral antenna with 3.3 cm ID and 6 cm OD

Cosmological perturbations in Palatini modified gravity

Two approaches to the study of cosmological density perturbations in modified theories of Palatini gravity have recently been discussed. These utilise, respectively, a generalisation of Birkhoff's theorem and a direct linearization of the gravitational field equations. In this paper these approaches are compared and contrasted. The general form of the gravitational lagrangian for which the two frameworks yield identical results in the long-wavelength limit is derived. This class of models includes the case where the lagrangian is a power-law of the Ricci curvature scalar. The evolution of density perturbations in theories of the type $f(R)=R-c /R^ b$ is investigated numerically. It is found that the results obtained by the two methods are in good agreement on sufficiently large scales when the values of the parameters (b,c) are consistent with current observational constraints. However, this agreement becomes progressively poorer for models that differ significantly from the standard concordance model and as smaller scales are considered

Recurrence of Type 1 Diabetes After Simultaneous Pancreas-Kidney Transplantation, Despite Immunosuppression, Is Associated With Autoantibodies and Pathogenic Autoreactive CD4 T-Cells

ObjectiveTo investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients.Research design and methodsWe monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays.ResultsAutoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells.ConclusionsWe demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used

Curvature singularities, tidal forces and the viability of Palatini f(R) gravity

In a previous paper we showed that static spherically symmetric objects which, in the vicinity of their surface, are well-described by a polytropic equation of state with 3/2<Gamma<2 exhibit a curvature singularity in Palatini f(R) gravity. We argued that this casts serious doubt on the validity of Palatini f(R) gravity as a viable alternative to General Relativity. In the present paper we further investigate this characteristic of Palatini f(R) gravity in order to clarify its physical interpretation and consequences.Comment: 15 pages. CQG in press. Part of the material moved to an appendix, discussion on the meV scale predictions of Palatini f(R) gravity adde

the CUTHIVAC-001 randomized trial

Targeting of different tissues via transcutaneous (TC), intradermal (ID) and intramuscular (IM) injection has the potential to tailor the immune response to DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1 negative volunteers we investigate whether the site and mode of DNA vaccination influences the quality of the cellular immune responses. We adopted a strategy of concurrent immunization combining IM injection with either ID or TC administration. As a third arm we assessed the response to IM injection administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B clade fusion protein designed to induce cellular immunity. The vaccine and regimens were well tolerated. We observed differential shaping of vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM + EP promoted strong IFN-γ responses and potent viral inhibition. ID + IM without EP resulted in a similar pattern of response but of lower magnitude. By contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated phenotype, associated with mucosal and epidermal protection. Whilst preliminary, these results offer new perspectives for differential shaping of desired cellular immunity required to fight the wide range of complex and diverse infectious diseases and cancers

Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin

Immune responses to autoantigens are in part controlled by deletion of autoreactive cells through genetically regulated selection mechanisms. We have directly analyzed peripheral CD4+ proinsulin (PI) 76–90 (SLQPLALEGSLQKRG)-specific T cells using soluble fluorescent major histocompatibility complex class II tetramers. Subjects with type I diabetes and healthy controls with high levels of peripheral proinsulin-specific T cells were characterized by the presence of a disease-susceptible polymorphism in the insulin variable number of tandem repeats (INS-VNTR) gene. Conversely, subjects with a ‘protective' polymorphism in the INS-VNTR gene had nearly undetectable levels of proinsulin tetramer-positive T cells. These results strongly imply a direct relationship between genetic control of autoantigen expression and peripheral autoreactivity, in which proinsulin genotype restricts the quantity and quality of the potential T-cell response. Using a modified tetramer to isolate low-avidity proinsulin-specific T cells from subjects with the susceptible genotype, transcript arrays identified several induced pro-apoptotic genes in the control, but not diabetic subjects, likely representing a second peripheral mechanism for maintenance of tolerance to self antigens