Mitosene-DNA adducts. Characterization of two major DNA monoadducts formed by 1,10-bis(acetoxy)-7-methoxymitosene upon reductive activation

Reductive activation of racemic 1,10-bis(acetoxy)-7-methoxymitosene WV15 in the presence of DNA, followed by enzymatic digestion and HPLC analysis, revealed the formation of various DNA adducts. Reduction is a necessary event for adduct formation to occur. This reductive activation was performed under hypoxic conditions in various ways:  (1) chemically, using a 2-fold excess of sodium dithionite (Na2S2O4), (2) enzymatically using NADH-cytochrome c reductase, (3) electrochemically on a mercury pool working electrode, and (4) catalytically, using a H2/PtO2 system. Five different mitosene−DNA adducts were detected. These adducts were also present when poly(dG-dC) was used instead of DNA, but were absent with poly(dA-dT). All were shown to be adducts of guanine. Reduction of 1,10-dihydroxymitosene WV14 in the presence of DNA did not result in detectable adduct formation, demonstrating the importance of good leaving groups for efficient adduct formation by these mitosenes. Finally, two of the adducts were isolated and their structures elucidated, using mass spectrometry, 1H NMR and circular dichroism (CD). The structures were assigned as the diastereoisomers N2-(1‘ ‘-n-hydroxymitosen-10‘ ‘-yl), 2‘-deoxyguanosine (n = α or β). These type of adducts, in which the mitosene C-10 is covalently bonded to the N-2 of a guanosylic group, are different from the well-known mitomycin C 2‘-deoxyguanosine monoadducts, that is linked via the mitomycin C C-1 position, demonstrating that the order of reactivity of the C-1 and C-10 in these mitosenes is reversed, as compared to mitomycin C. The 7-methoxy substituent of WV15 is a likely factor causing this switch. Evidence is presented that the 7-substituent of mitosenes also influences their DNA alkylation site. Adducts 4 and 5 represent the first isolated and structurally characterized covalent adducts of DNA and a synthetic mitosene

Cannibalism, warfare, and drought in the Mesa Verde region during the twelfth century A.D.

The existence of cannibalism has emerged as one of the most controversial issues in the archaeology of the American Southwest. In this paper, we examine this issue by presenting the results of our investigation at 5MT10010, a small early Pueblo III habitation site in southwestern Colorado. Battered, broken bones from seven individuals were discovered in two adjacent pithouses at 5MT10010. Mixed and incomplete remains of four adults and an adolescent were recovered from the floor and ventilator shaft of one pithouse; the remains of two subadults were found on the floor and in various subfeatures of the second. Cut marks and percussion scars implicate humans in the disarticulation and reduction of these bodies. Evidence of heat exposure on some bone fragments and laboratory analyses of a human coprolite recovered from one of the pithouses support the interpretation that people prepared and consumed human body parts. The discovery of disarticulated human remains at 5MT10010 is one of a number of similar finds in the northern Southwest. Analysis of cases from the Mesa Verde region indicates a sharp increase in cannibalism around A.D. 1150, a time of drought and the collapse of the Chaco system. The causes, consequences, and nature of this apparent outbreak of cannibalism are examined in light of 5MT10010 and other recent finds

EUHASS: The European Haemophilia Safety Surveillance system

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Global and Local D-vortices

Codimension-two objects on a system of brane-antibrane are studied in the context of Born-Infeld type effective field theory with a complex tachyon and U(1)$\times$U(1) gauge fields. When the radial electric field is turned on in D2${\bar {\rm D}}$2, we find static regular global and local D-vortex solutions which could be candidates of straight cosmic D-strings in a superstring theory. A natural extension to DF-strings is briefly discussed.Comment: 24 pages, 10 eps figure

Spontaneous Spin Polarized Currents in Superconductor-Ferromagnetic Metal Heterostructures

We study a simple microscopic model for thin, ferromagnetic, metallic layers on semi-infinite bulk superconductor. We find that for certain values of the exchange spliting, on the ferromagnetic side, the ground states of such structures feature spontaneously induced spin polarized currents. Using a mean-field theory, which is selfconsistent with respect to the pairing amplitude $\chi$, spin polarization $\vec{m}$ and the spontaneous current $\vec{j}_s$, we show that not only there are Andreev bound states in the ferromagnet but when their energies $E_n$ are near zero they support spontaneous currents parallel to the ferromagnetic-superconducting interface. Moreover, we demonstrate that the spin-polarization of these currents depends sensitively on the band filling.Comment: 4 pages, 5 Postscript figures (included

Spin-polarized transport and Andreev reflection in semiconductor/superconductor hybrid structures

We show that spin-polarized electron transmission across semiconductor/superconductor (Sm/S) hybrid structures depends sensitively on the degree of spin polarization as well as the strengths of potential and spin-flip scattering at the interface. We demonstrate that increasing the Fermi velocity mismatch in the Sm and S regions can lead to enhanced junction transparency in the presence of spin polarization. We find that the Andreev reflection amplitude at the superconducting gap energy is a robust measure of the spin polarization magnitude, being independent of the strengths of potential and spin-flip scattering and the Fermi velocity of the superconductor.Comment: 4 pages, 2 figure

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Data-driven definitions for active and structural MRI lesions in the sacroiliac joint in spondyloarthritis and their predictive utility

Objectives. To determine quantitative SI joint MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial SpA (axSpA) and that predict clinical diagnosis.Methods. The Assessment of SpondyloArthritis international Society (ASAS) MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises where (A) 169 cases and 7 central readers; (B) 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SI joint quadrants or slices with bone marrow oedema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with >= 95% specificity were analysed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPVs/NPVs) and selecting cut-offs with PPV >= 95%.Results. Active or structural lesions typical of axSpA on MRI had PPVs >= 95% for clinical diagnosis of axSpA. Cut-offs that best reflected a definite active lesion typical of axSpA were either >= 4 SI joint quadrants with BME at any location or at the same location in >= 3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of >= 3 SI joint quadrants with erosion or >= 5 with fat lesions, erosion at the same location for >= 2 consecutive slices, fat lesions at the same location for >= 3 consecutive slices, or presence of a deep (i.e. >1 cm depth) fat lesion.Conclusion. We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPVs for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research.Pathophysiology and treatment of rheumatic disease

Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays

Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of prime importance in probing new physics. Here 7421 +/- 105 signal events from the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A time-dependent fit to the data yields a value of phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201