[en] The authors report on a search for flavor-changing neutral current decays of B mesons B → μ⁺μ^-K^± and B → μ⁺μ^-K*⁰ using data obtained in the Collider Detector at Fermilab (CDF) 1992--1993 data taking run. To reduce the amount of background in the data the authors use precise tracking information from the CDF silicon vertex detector to pinpoint the location of the decay vertex of the B candidate, and accept only events which have a large decay time. They compare this data to a B meson signal obtained in a similar fashion, but where the muon pairs originate from ψ decays, and calculate the relative branching ratios. In absence of any indication of flavor-changing neutral current decays they set an upper limits of BR(B → μ⁺μ^-K^±) < 1.1 x 10^-5, and BR(B → μ⁺μ^-K*⁰) < 2.1 x 10^-5 at 90% confidence level, which are consistent with Standard Model expectations but leave little room for non-standard physics

[en] Full text: Ionizing radiation induces DNA lesions that lead to the activation of complex damage response pathways in mammalian cells. In one of these pathways the CDK inhibitor p21 is induced via stabilization of TP53. In addition, p21 was shown to accumulate at the sites of severe heavy ion-induced DNA damage [Jakob et al., 2000; Scholz et al., 2001]. These p21 foci appeared immediately after heavy ion irradiation, suggestive for a TP53-independent response. We intended to better understand the function of p21 at these high LET-induced DNA lesions. A role for p21 in DNA repair was studied by comparing HCT116 p21^-/- HCT116 p21^wt cells in their radiosensitivity (colony formation) as well as in their ability to rejoin DSBs after ionizing radiation. However, neither the fraction of cells surviving nor the kinetics of DSB rejoining were affected by the loss of p21. Therefore, we speculated that p21 might be involved in recognizing damaged DNA sites. To investigate the behaviour of the p21 protein within its foci, protein synthesis and proteasomal degradation were inhibited in normal human fibroblasts. Using Western blot technique, we determined the p21 turnover time to be approximately 55 min in these cells. Furthermore, protein synthesis was not required for p21 foci formation, and p21 protein synthesized either before or after irradiation was able to accumulate at the damaged DNA sites. When p21 synthesis was inhibited during and up to 3 h following irradiation, newly synthesized p21 protein still was able to form foci. In addition, the formation and the persistence of the p21 foci were not altered when the p21-level was artificially increased by inhibition of the proteasome. Our results indicate that the p21 focus most likely is not a static entity. Studies to elucidate a role for p21 in the early recognition of complex DNA lesions are currently being performed

[en] Flavor-changing neutral current decays of B mesons B → μ⁺μ^-K^± and B → μ⁺μ^-K^*0 are searched for using data obtained in the Collider Detector at Fermilab (CDF) [5] 1992-1993 data taking run. B candidates with two nonresonant muons and one or two tracks are investigated and this lack events is compared with a B meson signal obtained in a similar fashion, but where the muon pairs originate from ψ decays. In absence of any indication of flavor-changing neutral current decays an upper is set limits of BR(B → μ⁺μ^-K^±) < 1.0 x 10^-5, and BR(B → μ⁺μ^-K^*0) < 2.5 x 10^-5 at 90% confidence level. (author)

[en] Full text: The biological effectiveness of charged particle radiation is based on physical parameters like track structure and on the cellular response to the more complex types of lesions induced. Using immunofluorescence staining and confocal microscopy we have revealed the extremely localized accumulation of repair-related proteins at the sites of heavy ion-induced DNA damage in nuclei of human fibroblasts. The cell cycle protein p21 (CDKN1A) is a very early participant in this response, accumulating to foci of dynamic structure that form independently of the transactivation by TP53. The pattern of p21 accumulation directly reflects the microscopic distribution of the dose deposited for different radiation types. A new irradiation set-up, characterized by a small angle between the incident beam and the cell monolayer, extended the radiation track length and allowed to visualize the spatial distribution of protein aggregates along the ion trajectories. The particle tracks are imaged as parallel streaks of focal protein signals within the nuclei. In addition to p21, the distribution of repair proteins associating to sites of excision repair (i.e. PCNA) or DSB processing (i.e. hMre11 and TP53) was investigated in this way as a function of particle's LET. Immunostained γ-H2AX was utilized to visualize the formation of DSBs. The comparison of intensity profiles along the ion tracks revealed a strict spatial correlation for all the proteins studied. The patterns of protein clusters generated along the particle trajectories were inhomogeneous, but strikingly similar for ion beams from carbon to uranium, despite the wide range of particle energies and LETs and the greatly differing densities of lesions induced. The results point out the importance of chromatin organization in the localization of repair proteins to sites of damage

No abstract available

[en] We report on a search for flavor-changing neutral current decays of B mesons into γγK^* and γγK± using data obtained in the Collider Detector at Fermilab (CDF) 1992 endash 1993 data taking run. To reduce the amount of background in our data we use precise tracking information from the CDF silicon vertex detector to pinpoint the location of the decay vertex of the B candidate, and accept only events which have a large decay time.We compare this data to a B meson signal obtained in a similar fashion, but where the muon pairs originate from ψ decays, and calculate the relative branching ratios. In the absence of any indication of flavor-changing neutral current decays we set an upper limits of BR(B implies μμK^±) much-gt 3.5x10^-5, and BR(B implies μμK^*)much-gt 5.1x10^-5 at 90% confidence level, which are consistent with Standard Model expectations but leave little room for non-standard physics. copyright 1995 American Institute of Physics

[en] Short communication

[en] Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 domain that is known to interfere with the ability to suppress PCD (BCL-X L gly159ala). We also developed stable transfectants of TK6 cells that express a dominant negative caspase-9 that suppresses PCD. The results to date indicate that the mutated form of BCL-X L (gly159ala) does not suppress x-ray-induced PCD in TK6 cells, but it elevates radiation-induced TK1 mutant frequencies to the same extent as high level expression of wild-type BCL-X L . These data suggest that the anti-apoptotic function of BCL-2 family proteins is not required to elevate radiation mutagenesis. Separate experiments using TK6 cells that express a dominant negative caspase-9 indicate that this protein inhibits x-ray-induced PCD but TK1 mutant frequencies are not elevated. Taken together, the results suggest there is a separate function of BCL-2 family proteins that elevates radiation-induced mutagenesis independent of the well-known anti-apoptotic effect of these proteins of importance in human carcinogenesis

[en] Purpose: to compare the reproducibility (r) of CT value measurement of pulmonary nodules using volumetry software (LungCare, LC) and manual ROIs (mROI). Materials and methods: 54 artificial nodules in a chest phantom were scanned three times with CT. CT values were measured with LC and mROI. The intrascan-r was assessed with three measurements in the first scan, and the interscan-r with measurements in three consecutive scans (one observer). Intrascan-r und interobserver-r (two obs.) were assessed in the first scan and in contrast-enhanced CT of 51 nodules from 15 patients (kernels b50f and b80f). Intrascan-r and interscan-r were described as the mean range and interobserver-r as the mean difference of CT values. The significance of differences was tested using t-test and sign test. Results: reproducibility was significantly higher for volumetry-based measurements in both artificial and patient nodules (range 0.11 vs. 6.16 HU for intrascan-r, 2.22 vs. 7.03 HU for interscan-r, difference 0.11 vs. 18.42 HU for interobserver-r; patients: 1.78 vs. 13.19 HU (b50f-Kernel) and 1.88 vs. 27.4 HU (b80f-Kernel) for intrascan-r, 3.71 vs. 22.43 HU for interobserver-r). Absolute CT values differed significantly between convolution kernels (pat./mROI: 29.3 [b50f] and 151.9 HU [b80f] pat./LC: 5 [b50f] and 147 HU [b80f]). Conclusion: the reproducibility of volumetry-based measurements of CT values in pulmonary nodules is significantly higher and should therefore be recommended, e.g. in dynamic chest CT protocols. Reproducibility does not depend on absolute CT values. (orig.)

[en] We present the results of a search in bar p p collisions at √s =1.8 TeV for the top quark decaying to a charged Higgs bosson (H^±). We search for dilepton final states from the decay chain t bar t→HH (or HW, or WW)+b bar b→ll+X. In a sample of 19.3 pb^-1 collected during 1992--93 with the Collider Detector at Fermilab, we observe 2 events with a background estimation of 3.0±1.0 events. Limits at 95% C.L. in the (M_top,M_H^±) plane are presented. For the case M_top< M_W+M_b, we exclude at 95% C.L. the entire (M_top,M_H±) plane for the branching ratio B(H→τν) larger than 75%. We also interpret the results in terms of the parameter tanβ of two-Higgs-doublet models