Purpose: To (1) develop Monte Carlo applications for the geometry and particle transport in the treatment head of a compact coaxial plasma proton accelerator and (2) quantify the sensitivity of the ...output particle flux and dose distributions on the energy and angular spread of the input proton phase space. Method and Materials: Geant4 v4.9.3 was employed to simulate a plasma proton treatment head geometry including the beam collimator the magnetic field region and the energy selector. The energy spectrum assumed a Gaussian distribution centered at Emax=200MeV and the full width at half maximum (FWHM) was 0% 12.5% 25% 37.5% and 50% of Emax. The angular spread of the input proton beam was considered to be 0° 15° and 20° respectively. Flux and dose calculations were performed using a phase space implemented at the energy selector exit plane and a voxelized water phantom respectively. Results: For a fixed angular spread the output particle flux is fairly constant as the energy spectrum becomes broader while for a fixed energy spread the flux decreases significantly with increasing angular spread. The decrease is 10 times for 15° and 40 times for 20° angular spread. Dose measurements show that 200MeV protons even with a broad energy spectrum are preferable to photons when low entrance dose and conformal distal edge falloff are desired. The energy spread translates into a spread out Bragg peak used clinically without the introduction of any scattering devices in the beam path. Conclusions: This study shows that the delivered proton flux is highly sensitive to the angular spectrum of the input plasma accelerated protons and dose is sensitive to the spread of the energy spectrum. Monte Carlo simulations of beam characteristics for compact plasma proton accelerators provide important design parameters for the development of the next generation proton therapy units.
Abstract Many SIV isolates can employ the orphan receptor GPR15 as coreceptor for efficient entry into transfected cell lines, but the role of endogenously expressed GPR15 in SIV cell tropism is ...largely unclear. Here, we show that several human B and T cell lines express GPR15 on the cell surface, including the T/B cell hybrid cell line CEMx174, and that GPR15 expression is essential for SIV infection of CEMx174 cells. In addition, GPR15 expression was detected on subsets of primary human CD4+ , CD8+ and CD19+ peripheral blood mononuclear cells (PBMCs), respectively. However, GPR15+ PBMCs were not efficiently infected by HIV and SIV, including cells from individuals homozygous for the defective Δ32 ccr5 allele. These results suggest that GPR15 is coexpressed with CD4 on PBMCs but that infection of CD4+ , GPR15+ cells is not responsible for the well documented ability of SIV to infect CCR5− blood cells.
In this case series, three unrelated male housemate cats were treated repeatedly with injections of medroxyprogesterone acetate (MPA) for intercat aggression and urinary house soiling. All three cats ...subsequently developed multiple recurrent mammary adenocarcinomas and underwent numerous surgical resections. This report describes the clinical, histopathological and immunohistochemical findings in these three cats and highlights the potential for mammary carcinomas to develop in male cats years after receiving MPA injections. Extended survival times and a long delay between the administration of the progestin injections and the onset of mammary neoplasia are noted. Estrogen and progesterone receptor staining was performed on some of the tumors and the complex role of hormones in the pathogenesis and the prognosis of feline mammary carcinoma is discussed. Clinicians using MPA should institute life-long surveillance of their feline patients for mammary tumors.
Abstract The C-type lectin DC-SIGN binds to oligosaccharides on the human and simian immunodeficiency virus (HIV, SIV) envelope glycoproteins and promotes infection of susceptible cells. Here, we ...show that DC-SIGN recognizes glycans involved in SIV sensitivity to neutralizing antibodies and that binding to DC-SIGN confers neutralization resistance to an otherwise sensitive SIV variant. Moreover, we provide evidence that mannose-binding lectin (MBL) can interfere with HIV-1 neutralization by the carbohydrate-specific antibody 2G12.
CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed ...that CIRE/mDC-SIGN is indeed on the surface of some CD4+, CD4- 8- DCs and plasmacytoid pre-DCs, but not on CD8+ DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell-DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.
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