463 research outputs found

    Preventive Strategies in Epithelial Ovarian Cancer

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    On the co-existence of chemically peculiar Bp stars, slowly pulsating B stars and constant B stars in the same part of the H-R diagram

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    Aims. In order to better model massive B-type stars, we need to understand the physical processes taking place in slowly pulsating B (SPB) stars, chemically peculiar Bp stars, and non-pulsating normal B stars co-existing in the same part of the H-R diagram. Methods. We carry out a comparative study between samples of confirmed and well-studied SPB stars and a sample of well-studied Bp stars with known periods and magnetic field strengths. We determine their evolutionary state using accurate HIPPARCOS parallaxes and Geneva photometry. We discuss the occurrence and strengths of magnetic fields as well as the occurrence of stellar pulsation among both groups. Further, we make a comparison of Geneva photometric variability for both kinds of stars. Results. The group of Bp stars is significantly younger than the group of SPB stars. Longitudinal magnetic fields in SPB stars are weaker than those of Bp stars, suggesting that the magnetic field strength is an important factor for B type stars to become chemically peculiar. The strongest magnetic fields appear in young Bp stars, indicating a magnetic field decay in stars at advanced ages. Rotation periods of Bp and pulsation periods of SPB stars are of the same order and the behaviour of Geneva photometric variability of some Bp stars cannot be distinguished from the variability of SPB stars, illustrating the difficulty to interpret the observed variability of the order of days for B-type stars. We consider the possibility that pulsation could be responsible for the variability among chemically peculiar stars. In particular, we show that a non-linear pulsation model is not excluded by photometry for the Bp star HD175362.Comment: Accepted for publication in Astronomy & Astrophysics on 29/01/2007, 8 pages, 9 figure

    Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity.

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    The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the growth of multiple types of subcutaneously transplanted tumors in wild-type, but not FAP-null immune-competent syngeneic mice. The antitumor effects could be augmented by multiple injections of the CAR T cells, by using CAR T cells with a deficiency in diacylglycerol kinase, or by combination with a vaccine. A major mechanism of action of the muFAP-CAR T cells was the augmentation of the endogenous CD8(+) T-cell antitumor responses. Off-tumor toxicity in our models was minimal following muFAP-CAR T-cell therapy. In summary, inhibiting tumor growth by targeting tumor stroma with adoptively transferred CAR T cells directed to FAP can be safe and effective, suggesting that further clinical development of anti-human FAP-CAR is warranted

    Characterization of Gravitational Microlensing Planetary Host Stars

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    The gravitational microlensing light curves that reveal the presence of extrasolar planets generally yield the planet-star mass ratio and separation in units of the Einstein ring radius. The microlensing method does not require the detection of light from the planetary host star. This allows the detection of planets orbiting very faint stars, but it also makes it difficult to convert the planet-star mass ratio to a value for the planet mass. We show that in many cases, the lens stars are readily detectable with high resolution space-based follow-up observations in a single passband. When the lens star is detected, the lens-source relative proper motion can also be measured, and this allows the masses of the planet and its host star to be determined and the star-planet separation can be converted to physical units. Observations in multiple passbands provide redundant information, which can be used to confirm this interpretation. For the recently detected super-Earth planet, OGLE-2005-BLG-169Lb, we show that the lens star will definitely be detectable with observations by the Hubble Space Telescope (HST) unless it is a stellar remnant. Finally, we show that most planets detected by a space-based microlensing survey are likely to orbit host stars that will be detected and characterized by the same survey.Comment: accepted for publication in ApJ, May 10, 200

    Species identification of European forest pathogens of the genus Milesina (Pucciniales) using urediniospore morphology and molecular barcoding including M. woodwardiana sp. nov

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    Species of rust fungi of the genus Milesina (Pucciniastraceae, Pucciniales) are distributed mainly in northern temperate regions. They host-alternate between needles of fir (Abies spp.) and fronds of ferns (species of Polypodiales). Milesina species are distinguished based on host taxonomy and urediniospore morphology. In this study, 12 species of Milesina from Europe were revised. Specimens were examined by light and scanning electron microscopy for urediniospore morphology with a focus on visualising germ pores (number, size and position) and echinulation. In addition, barcode loci (ITS, nad6, 28S) were used for species delimitation and for molecular phylogenetic analyses. Barcodes of 72 Milesina specimens were provided, including 11 of the 12 species. Whereas urediniospore morphology features were sufficient to distinguish all 12 Milesina species except for 2 (M. blechni and M. kriegeriana), ITS sequences separated only 4 of 11 species. Sequencing with 28S and nad6 did not improve species resolution. Phylogenetic analysis, however, revealed four phylogenetic groups within Milesina that also correlate with specific urediniospore characters (germ pore number and position and echinulation). These groups are proposed as new sections within Milesina (sections Milesina, Vogesiacae M. Scholler & Bubner, sect. nov., Scolopendriorum M. Scholler & Bubner, sect. nov. and Carpaticae M. Scholler & Bubner, sect. nov.). In addition, Milesina woodwardiana Buchheit & M. Scholler, sp. nov. on Woodwardia radicans, a member of the type section Milesina, is newly described. An identification key for European Milesina species, based on urediniospore features, is provided

    Trumpler 16-26: A New Centrifugal Magnetosphere Discovered via SDSS/APOGEE H-band Spectroscopy

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    We report the discovery of a new example of the rare class of highly magnetized, rapidly rotating, helium enhanced, early B stars that produce anomalously wide hydrogen emission due to a centrifugal magnetosphere (CM). The star is Trumpler 16-26, a B1.5 V member of the Trumpler 16 open cluster. A CM was initially suspected based on hydrogen Brackett series emission observed in SDSS/APOGEE HH-band spectra. Similar to the other stars of this type, the emission was highly variable and at all times remarkable due to the extreme velocity separations of the double peaks (up to 1300 km s1^{-1}.) Another clue lay in the TESS lightcurve, which shows two irregular eclipses per cycle when phased with the likely 0.9718115 day rotation period, similar to the behavior of the well known CM host star σ\sigma Ori E. To confirm a strong magnetic field and rotation-phase-locked variability, we initiated a follow-up campaign consisting of optical spectropolarimetry and spectroscopy. The associated data revealed a longitudinal magnetic field varying between 3.1-3.1 and +1.6+1.6 kG with the period found from photometry. The optical spectra confirmed rapid rotation (vsini=195v \sin i=195 km s1^{-1}), surface helium enhancement, and wide, variable hydrogen emission. Tr16-26 is thus confirmed as the 20th^{\rm th} known, the fourth most rapidly rotating, and the faintest CM host star yet discovered. With a projected dipole magnetic field strength of Bd>11B_{\rm d}>11 kG, Tr16-26 is also among the most magnetic CM stars

    Systematic Evaluation of Candidate Blood Markers for Detecting Ovarian Cancer

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    Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging. We evaluated the performance of a set of candidate blood markers and combinations of these markers in detecting serous ovarian cancer.We selected 14 candidate blood markers of serous ovarian cancer for which assays were available to measure their levels in serum or plasma, based on our analysis of global gene expression data and on literature searches. We evaluated the performance of these candidate markers individually and in combination by measuring them in overlapping sets of serum (or plasma) samples from women with clinically detectable ovarian cancer and women without ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of the 14 candidate markers--MUC16, WFDC2, MSLN and MMP7--warrant further evaluation in precious serum specimens collected months to years prior to clinical diagnosis to assess their utility in early detection. We also reported differences in the performance of these candidate blood markers across histological types of epithelial ovarian cancer.By systematically analyzing the performance of candidate blood markers of ovarian cancer in distinguishing women with clinically apparent ovarian cancer from women without ovarian cancer, we identified a set of serum markers with adequate performance to warrant testing for their ability to identify ovarian cancer months to years prior to clinical diagnosis. We argued for the importance of sensitivity at high specificity and of magnitude of difference in marker levels between cases and controls as performance metrics and demonstrated the importance of stratifying analyses by histological type of ovarian cancer. Also, we discussed the limitations of studies (like this one) that use samples obtained from symptomatic women to assess potential utility in detection of disease months to years prior to clinical detection

    Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer.

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    OBJECTIVE: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics of healthy women who are likely candidates for an ovarian cancer screening program. METHODS: We analyzed serum CA125, mesothelin, and HE4 levels in a sample of 155 healthy postmenopausal women at increased risk for developing ovarian cancer based on personal and family cancer history. Information on reproductive, family and medical histories, lifestyle factors, and anthropometry was collected by self-report. Twenty-two factors were examined using univariate and multiple linear regression models for the three biomarker levels. RESULTS: In the multivariate models, CA125 levels were significantly higher in women who had used talcum powder (P = 0.02) and were lower in women who were parous (P = 0.05). Mesothelin levels were significantly higher in older women (P = 0.01) and lower in heavier women (P = 0.03). HE4 levels were higher in older women (P = 0.001) and in women who began menstruating at an older age (P = 0.03). CONCLUSIONS: CA125, mesothelin, and HE4 levels in healthy, postmenopausal women at increased risk for ovarian cancer are significantly associated with a few ovarian cancer risk factors. Since the effects of these personal characteristics on these serum markers are not large, their incorporation in screening algorithms may be unnecessary. This is true especially if a longitudinal algorithm is used because the marker level at the previous screen reflects personal characteristics such as age, body mass index, and age of menarche. Understanding the influence of personal factors on levels of novel early detection markers in healthy, unaffected women may have clinical utility in interpreting biomarker levels

    Chemical dissociation of human awareness: focus on non-competitive NMDA receptor antagonists

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    Since the mid-1950s the pharmaceutical industry has developed a number of chemicals, including phencyclidine, ketamine and related arylcyclohexylamines (PCE and TCP), dizocilpine (MK-801), N-allylnormetazocine [ NANM, (±)SKF-10,047], etoxadrol, dioxadrol and its enantiomers dexoxadrol and levoxadrol, which produce a constellation of unusual behavioral effects in animals and man. The compounds best studied in humans are phencyclidine and ketamine. They produce a remarkable dose-dependent dissociation of awareness. All of these substances are now known to be non-competitive antagonists of NMDA receptors of glutamic acid. They act in the NMDA receptor ion channel. One can conclude, on the basis of the effects observed with these agents, that glutamic acid and related excitatory amino acids are extremely important in the maintenance of human awareness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68872/2/10.1177_026988119200600312.pd
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