7,998 research outputs found

    Steroid sulfatase:a pivotal player in estrogen synthesis and metabolism

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    International audienceSteroid sulfatase plays a pivotal role in regulating the formation of biologically active steroids from inactive steroid sulfates. It is responsible for the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone, respectively, both of which can be subsequently reduced to steroids with estrogenic properties (i.e. estradiol and androstenediol) that can stimulate the growth of tumors in hormone-responsive tissues of the breast, endometrium and prostate. Hence, the action of steroid sulfatase is implicated in physiological processes and pathological conditions. It has been five years since our group last reviewed the important role of this enzyme in steroid synthesis and the progress made in the development of potent inhibitors of this important enzyme target. This timely review therefore concentrates on recent advances in steroid sulfatase research, and summarises the findings of clinical trials with Irosustat (BN83495), the only steroid sulfatase inhibitor that is being trialed in postmenopausal women with breast or endometrial cancer

    Replication of Known Dental Characteristics in Porcine Skin: Emerging Technologies for the Imaging Specialist

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    This study demonstrates that it is sometimes possible to replicate patterns of human teeth in pig skin and determine scientifically that a given injury pattern (bite mark) correlates with the dentitions of a very small proportion of a population dataset, e.g., 5 percent or even 1 percent. The authors recommend building on the template of this research with a sufficiently large database of samples that reflects the diverse world population. They also envision the development of a sophisticated imaging software application that enables forensic examiners to insert parameters for measurement, as well as additional methods of applying force to produce bite marks for research. The authors further advise that this project is applied science for injury pattern analysis and is only foundational research that should not be cited in testimony and judicial procedures. It supplements but does not contradict current guidelines of the American Board of Forensic Odontology regarding bite mark analysis and comparisons. A much larger population database must be developed. The project’s methodology is described in detail, accompanied by 11 tables and 41 figures

    A Methodology for Three-Dimensional Quantification of Anterior Tooth Width

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    The use of cone-beam computed tomography (CBCT) technology has been shown to be more accurate in measuring individual incisor tooth widths than the use of wax exemplars. There were fewer differences by investigators using CBCT than others using an F-test in a mixed model of the measurement differences of investigators, wax type, and which tooth was measured. In addition, the frequency of outliers was less in the CBCT method (a total of 5) as compared to the two-dimensional measurements in ether Aluwax (a total of 8) or Coprwax (a total of 12). Both results indicate that CBCT measurements accounted more precisely for tooth width and level of eruption

    Bell inequality for pairs of particle-number-superselection-rule restricted states

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    Proposals for Bell inequality tests on systems restricted by superselection rules often require operations that are difficult to implement in practice. In this paper, we derive a new Bell inequality, where pairs of states are used to by-pass the superselection rule. In particular, we focus on mode entanglement of an arbitrary number of massive particles and show that our Bell inequality detects the entanglement in the pair when other inequalities fail. However, as the number of particles in the system increases, the violation of our Bell inequality decreases due to the restriction in the measurement space caused by the superselection rule. This Bell test can be implemented using techniques that are routinely used in current experiments.Comment: 9 pages, 6 figures; v2 is the published versio

    Thermal fluctuation field for current-induced domain wall motion

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    Current-induced domain wall motion in magnetic nanowires is affected by thermal fluctuation. In order to account for this effect, the Landau-Lifshitz-Gilbert equation includes a thermal fluctuation field and literature often utilizes the fluctuation-dissipation theorem to characterize statistical properties of the thermal fluctuation field. However, the theorem is not applicable to the system under finite current since it is not in equilibrium. To examine the effect of finite current on the thermal fluctuation, we adopt the influence functional formalism developed by Feynman and Vernon, which is known to be a useful tool to analyze effects of dissipation and thermal fluctuation. For this purpose, we construct a quantum mechanical effective Hamiltonian describing current-induced domain wall motion by generalizing the Caldeira-Leggett description of quantum dissipation. We find that even for the current-induced domain wall motion, the statistical properties of the thermal noise is still described by the fluctuation-dissipation theorem if the current density is sufficiently lower than the intrinsic critical current density and thus the domain wall tilting angle is sufficiently lower than pi/4. The relation between our result and a recent result, which also addresses the thermal fluctuation, is discussed. We also find interesting physical meanings of the Gilbert damping alpha and the nonadiabaticy parameter beta; while alpha characterizes the coupling strength between the magnetization dynamics (the domain wall motion in this paper) and the thermal reservoir (or environment), beta characterizes the coupling strength between the spin current and the thermal reservoir.Comment: 16 page, no figur

    Development of steroid sulfatase inhibitors

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    Disrupted functional brain network organization in patients with obstructive sleep apnea.

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    IntroductionObstructive sleep apnea (OSA) subjects show impaired autonomic, affective, executive, sensorimotor, and cognitive functions. Brain injury in OSA subjects appears in multiple sites regulating these functions, but the integrity of functional networks within the regulatory sites remains unclear. Our aim was to examine the functional interactions and the complex network organization of these interactions across the whole brain in OSA, using regional functional connectivity (FC) and brain network topological properties.MethodsWe collected resting-state functional magnetic resonance imaging (MRI) data, using a 3.0-Tesla MRI scanner, from 69 newly diagnosed, treatment-naïve, moderate-to-severe OSA (age, 48.3 ± 9.2 years; body mass index, 31 ± 6.2 kg/m(2); apnea-hypopnea index (AHI), 35.6 ± 23.3 events/h) and 82 control subjects (47.6 ± 9.1 years; body mass index, 25.1 ± 3.5 kg/m(2)). Data were analyzed to examine FC in OSA over controls as interregional correlations and brain network topological properties.ResultsObstructive sleep apnea subjects showed significantly altered FC in the cerebellar, frontal, parietal, temporal, occipital, limbic, and basal ganglia regions (FDR, P < 0.05). Entire functional brain networks in OSA subjects showed significantly less efficient integration, and their regional topological properties of functional integration and specialization characteristics also showed declined trends in areas showing altered FC, an outcome which would interfere with brain network organization (P < 0.05; 10,000 permutations). Brain sites with abnormal topological properties in OSA showed significant relationships with AHI scores.ConclusionsOur findings suggest that the dysfunction extends to resting conditions, and the altered FC and impaired network organization may underlie the impaired responses in autonomic, cognitive, and sensorimotor functions. The outcomes likely result from the prominent structural changes in both axons and nuclear structures, which occur in the condition

    The UV Continuum of Quasars: Models and SDSS Spectral Slopes

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    We measure long (2200-4000 ang) and short (1450-2200 ang) wavelength spectral slopes \alpha (F_\nu proportional to \nu^\alpha) for quasar spectra from the Sloan Digital Sky Survey. The long and short wavelength slopes are computed from 3646 and 2706 quasars with redshifts in the z=0.76-1.26 and z=1.67-2.07 ranges, respectively. We calculate mean slopes after binning the data by monochromatic luminosity at 2200 ang and virial mass estimates based on measurements of the MgII line width and 3000 ang continuum luminosity. We find little evidence for mass dependent variations in the mean slopes, but a significant luminosity dependent trend in the near UV spectral slopes is observed with larger (bluer) slopes at higher luminosities. The far UV slopes show no clear variation with luminosity and are generally lower (redder) than the near UV slopes at comparable luminosities, suggesting a slightly concave quasar continuum shape. We compare these results with Monte Carlo distributions of slopes computed from models of thin accretion disks, accounting for uncertainties in the mass estimates. The model slopes produce mass dependent trends which are larger than observed, though this conclusion is sensitive to the assumed uncertainties in the mass estimates. The model slopes are also generally bluer than observed, and we argue that reddening by dust intrinsic to the source or host galaxy may account for much of the discrepancy.Comment: To be published in ApJ, 18 pages, 10 figure
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