Screening for germline DND1 mutations in testicular cancer patients

Although several observations suggest that a strong genetic predisposition to developing testicular germ cell tumors (TGCT) exists, no associated, highly penetrant germline mutations have been identified so far. In the 129/Sv mouse strain, a germline mutation in the DND1 gene has been shown to strongly increase the TGCT risk. We screened 272 men with TGCT (89% sporadic cases, 11% familial) for germline mutations in the human homologue of DND1. A single nucleotide substitution c.657C > G (p.Asp219Glu) was observed in a non-familial case of testicular embryonal carcinoma. The variant was also present in the patient’s asymptomatic father and two brothers, but not observed in 210 control chromosomes. The wild type DND1 allele was not lost in the patient’s tumor. In silico analysis of the variant predicts it to be non-pathogenic. We conclude that germline DND1 mutations are unlikely to contribute significantly to human testicular germ cell tumor susceptibility. The role of human DND1 in normal physiology and disease, however, is still virtually unknown and it therefore warrants further research

Spectropolarimetry of 3CR 68.1: A Highly Inclined Quasar

We present Keck spectropolarimetry of the highly polarized radio-loud quasar 3CR 68.1 (z=1.228, V=19). The polarization increases from 5 in the red (4000 A rest-frame) to >10% in the blue (1900 A rest-frame). The broad emission lines are polarized the same as the continuum, which shows that 3CR 68.1 is not a blazar as it has sometimes been regarded in the past. We also present measurements of the emission lines and a strong, blueshifted, associated absorption line system, as well as a detection at the emission-line redshift of Ca II K absorption, presumably from stars in the host galaxy. 3CR 68.1 belongs to an observationally rare class of highly polarized quasars that are neither blazars nor partially obscured radio-quiet QSOs. Taking into account 3CR 68.1's other unusual properties, such as its extremely red spectral energy distribution and its extreme lobe dominance, we explain our spectropolarimetric results in terms of unified models. We argue that we have a dusty, highly inclined view of 3CR 68.1, with reddened scattered (polarized) quasar light diluted by even more dust-reddened quasar light reaching us directly from the nucleus.Comment: 20 pages, includes 3 tables, 6 figures. Accepted by Ap

Double Lobed Radio Quasars from the Sloan Digital Sky Survey

We have combined a sample of 44984 quasars, selected from the Sloan Digital Sky Survey (SDSS) Data Release 3, with the FIRST radio survey. Using a novel technique where the optical quasar position is matched to the complete radio environment within 450", we are able to characterize the radio morphological make-up of what is essentially an optically selected quasar sample, regardless of whether the quasar (nucleus) itself has been detected in the radio. About 10% of the quasar population have radio cores brighter than 0.75 mJy at 1.4 GHz, and 1.7% have double lobed FR2-like radio morphologies. About 75% of the FR2 sources have a radio core (> 0.75 mJy). A significant fraction (~40%) of the FR2 quasars are bent by more than 10 degrees, indicating either interactions of the radio plasma with the ICM or IGM. We found no evidence for correlations with redshift among our FR2 quasars: radio lobe flux densities and radio source diameters of the quasars have similar distributions at low (mean 0.77) and high (mean 2.09) redshifts. Using a smaller high reliability FR2 sample of 422 quasars and two comparison samples of radio-quiet and non-FR2 radio-loud quasars, matched in their redshift distributions, we constructed composite optical spectra from the SDSS spectroscopic data. Based on these spectra we can conclude that the FR2 quasars have stronger high-ionization emission lines compared to both the radio quiet and non-FR2 radio loud sources. This is consistent with the notion that the emission lines are brightened by ongoing shock ionization of ambient gas in the quasar host as the radio source expands.Comment: 20 pages, 10 figures - some of which have been reduced in quality / size. Accepted for publication in the Astronomical Journa

Immunocytochemical analysis of cisplatin-induced platinum-DNA adducts with double-fluorescence video microscopy.

To detect low-level DNA platination, a sensitive immunocyto- and histochemical technique was developed using a polyclonal antibody. The antibody GPt, derived after immunization of rabbits with highly platinated DNA and purified with affinity chromatography, detected the main platinum (Pt)-containing intrastrand and interstrand adducts. Double-fluorescence microscopy image analysis was used to quantify Pt-DNA adducts with Hoechst 33258 fluorescence to locate the nuclei and with fluorescein isothiocyanate fluorescence to measure the immunosignal. A two- to five-fold dose-dependent difference in the level of cisplatin (CDDP)-induced Pt-DNA adducts between a CDDP-sensitive and -resistant human tumour cell line was detected. Large differences in Pt-DNA adduct levels after in vitro CDDP incubation between human buccal cells, lymphocytes and biopsies of different tumour types were observed. Pt-DNA adduct levels were fivefold higher in human testicular tumours than in colon tumours, representing CDDP-sensitive and -resistant tumours, respectively, in the clinic. These data suggest the possibility of predictive testing by measuring Pt-DNA adduct levels. Pt-DNA adducts in patients after treatment with CDDP were shown in normal buccal cells and in imprints of fresh tumour biopsies as well as in paraffin-embedded tumour cells. The analysis of Pt-DNA adducts at a single-cell level in small samples of normal and tumour cells during and/or after treatment is feasible with GPt and will hopefully enable more selective treatment of patients

Bivariate stochastic modeling of functional response with natural mortality

A correction due to Abbott (1925) is the standard method of dealing with control mortality in insect bioassay to estimate the mortality of an insect conditional on control mortality not having occurred. In this article a bivariate stochastic process for overall mortality is developed in which natural mortality and predation are jointly modeled to take account of the competing-risks associated with prey loss. The total mortality estimate from this model is essentially identical with that from more classical modeling. However, when predation loss is estimated in the absence of control mortality the results are somewhat different, with the estimate from the bivariate model being lower than that from using Abbott’s formula in conjunction with the classical model. It is argued that overdispersion in observed mortality data corresponds to correlated outcomes (death or survival) for the prey initially present, while Abbott’s correction relies implicitly on independence

Outcome of depression in later life in primary care: longitudinal cohort study with three years’ follow-up

Objectives To study the duration of depression, recovery over time, and predictors of prognosis in an older cohort (≥55 years) in primary care

Substructure lensing in galaxy clusters as a constraint on low-mass sterile neutrinos in tensor-vector-scalar theory: The straight arc of Abell 2390

Certain covariant theories of the modified Newtonian dynamics paradigm seem to require an additional hot dark matter (HDM) component - in the form of either heavy ordinary neutrinos or more recently light sterile neutrinos (SNs) with a mass around 11eV - to be relieved of problems ranging from cosmological scales down to intermediate ones relevant for galaxy clusters. Here we suggest using gravitational lensing by galaxy clusters to test such a marriage of neutrino HDM and modified gravity, adopting the framework of tensor-vector-scalar theory (TeVeS). Unlike conventional cold dark matter (CDM), such HDM is subject to strong phase-space constraints, which allows one to check cluster lens models inferred within the modified framework for consistency. Since the considered HDM particles cannot collapse into arbitrarily dense clumps and only form structures well above the galactic scale, systems which indicate the need for dark substructure are of particular interest. As a first example, we study the cluster lens Abell 2390 and its impressive straight arc with the help of numerical simulations. Based on our results, we outline a general and systematic approach to model cluster lenses in TeVeS which significantly reduces the calculation complexity. We further consider a simple bimodal lens configuration, capable of producing the straight arc, to demonstrate our approach. We find that such a model is marginally consistent with the hypothesis of 11eV SNs. Future work including more detailed and realistic lens models may further constrain the necessary SN distribution and help to conclusively assess this point. Cluster lenses could therefore provide an interesting discriminator between CDM and such modified gravity scenarios supplemented by SNs or other choices of HDM.Comment: 22 pages, 14 figures, 2 tables; minor changes to match accepted versio

Perioperative PET/CT lymphoscintigraphy and fluorescent real-time imaging for sentinel lymph node mapping in early staged colon cancer

Contains fulltext : 207332.pdf (publisher's version ) (Open Access