Experimental active and passive dosimetry systems for the NASA Skylab program

Active and passive dosimetry instrumentation to measure absorbed dose, charged particle spectra, and linear energy transfer spectra inside the command module and orbital workshop on the Skylab program were developed and tested. The active dosimetry system consists of one integral unit employing both a tissue equivalent ionization chamber and silicon solid state detectors. The instrument measures dose rates from 0.2 millirad/hour to 25 rads/hour, linear energy transfer spectra from 2.8 to 42.4 Kev/micron, and the proton and alpha particle energy spectra from 0.5 to 75 Mev. The active dosimeter is equipped with a portable radiation sensor for use in astronaut on-body and spacecraft shielding surveys during passage of the Skylab through significant space radiations. Data are transmitted in real time or are recorded by onboard spacecraft tape recorder for rapid evaluation of the radiation levels. The passive dosimetry systems consist of twelve (12) hard-mounted assemblies, each containing a variety of passive radiation sensors which are recoverable at the end of the mission for analysis

Observation of the Charge Symmetry Breaking d + d -> 4He + pi0 Reaction Near Threshold

We report the first observation of the charge symmetry breaking d + d -> 4He + pi0 reaction near threshold at the Indiana University Cyclotron Facility. Kinematic reconstruction permitted the separation of 4He + pi0 events from double radiative capture 4He + gamma + gamma events. We measured total cross sections for neutron pion production of 12.7 +- 2.2 pb at 228.5 MeV and 15.1 +- 3.1 pb at 231.8 MeV. The uncertainty is dominated by statistical errors.Comment: 7 pages, 2 figures, plain Te

A multi-detector array for high energy nuclear e+e- pair spectrosocopy

A multi-detector array has been constructed for the simultaneous measurement of energy- and angular correlation of electron-positron pairs produced in internal pair conversion (IPC) of nuclear transitions up to 18 MeV. The response functions of the individual detectors have been measured with mono-energetic beams of electrons. Experimental results obtained with 1.6 MeV protons on targets containing $^{11}$B and $^{19}$F show clear IPC over a wide angular range. A comparison with GEANT simulations demonstrates that angular correlations of $e^+e^-$ pairs of transitions in the energy range between 6 and 18 MeV can be determined with sufficient resolution and efficiency to search for deviations from IPC due to the creation and subsequent decay into $e^+e^-$ of a hypothetical short-lived neutral boson.Comment: 20 pages, 8 figure

Direct Repeat 6 from Human Herpesvirus-6B Encodes a Nuclear Protein that Forms a Complex with the Viral DNA Processivity Factor p41

The SalI-L fragment from human herpesvirus 6A (HHV-6A) encodes a protein DR7 that has been reported to produce fibrosarcomas when injected into nude mice, to transform NIH3T3 cells, and to interact with and inhibit the function of p53. The homologous gene in HHV-6B is dr6. Since p53 is deregulated in both HHV-6A and -6B, we characterized the expression of dr6 mRNA and the localization of the translated protein during HHV-6B infection of HCT116 cells. Expression of mRNA from dr6 was inhibited by cycloheximide and partly by phosphonoacetic acid, a known characteristic of herpesvirus early/late genes. DR6 could be detected as a nuclear protein at 24 hpi and accumulated to high levels at 48 and 72 hpi. DR6 located in dots resembling viral replication compartments. Furthermore, a novel interaction between DR6 and the viral DNA processivity factor, p41, could be detected by confocal microscopy and by co-immunoprecipitation analysis. In contrast, DR6 and p53 were found at distinct subcellular locations. Together, our data imply a novel function of DR6 during HHV-6B replication

Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer

The generation of antitumour immunity depends on the nature of dendritic cell (DC)–tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy

International study on inter-reader variability for circulating tumor cells in breast cancer

Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement.Methods: CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test.Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90).Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required

Theoretical methods for the calculation of Bragg curves and 3D distributions of proton beams

The well-known Bragg-Kleeman rule RCSDA = A dot E0p has become a pioneer work in radiation physics of charged particles and is still a useful tool to estimate the range RCSDA of approximately monoenergetic protons with initial energy E0 in a homogeneous medium. The rule is based on the continuous-slowing-down-approximation (CSDA). It results from a generalized (nonrelativistic) Langevin equation and a modification of the phenomenological friction term. The complete integration of this equation provides information about the residual energy E(z) and dE(z)/dz at each position z (0 <= z <= RCSDA). A relativistic extension of the generalized Langevin equation yields the formula RCSDA = A dot (E0 +E02/2M dot c2)p. The initial energy of therapeutic protons satisfies E0 << 2M dot c2 (M dot c2 = 938.276 MeV), which enables us to consider the relativistic contributions as correction terms. Besides this phenomenological starting-point, a complete integration of the Bethe-Bloch equation (BBE) is developed, which also provides the determination of RCSDA, E(z) and dE(z)/dz and uses only those parameters given by the BBE itself (i.e., without further empirical parameters like modification of friction). The results obtained in the context of the aforementioned methods are compared with Monte-Carlo calculations (GEANT4); this Monte-Carlo code is also used with regard to further topics such as lateral scatter, nuclear interactions, and buildup effects. In the framework of the CSDA, the energy transfer from protons to environmental atomic electrons does not account for local fluctuations.Comment: 97 pages review pape

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p((adjusted))=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p((adjusted))=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p((interaction))=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.Peer reviewe