Leading hadronic contribution to the muon magnetic moment from lattice QCD.

The standard model of particle physics describes the vast majority of experiments and observations involving elementary particles. Any deviation from its predictions would be a sign of new, fundamental physics. One long-standing discrepancy concerns the anomalous magnetic moment of the muon, a measure of the magnetic field surrounding that particle. Standard-model predictions1 exhibit disagreement with measurements2 that is tightly scattered around 3.7 standard deviations. Today, theoretical and measurement errors are comparable; however, ongoing and planned experiments aim to reduce the measurement error by a factor of four. Theoretically, the dominant source of error is the leading-order hadronic vacuum polarization (LO-HVP) contribution. For the upcoming measurements, it is essential to evaluate the prediction for this contribution with independent methods and to reduce its uncertainties. The most precise, model-independent determinations so far rely on dispersive techniques, combined with measurements of the cross-section of electron-positron annihilation into hadrons3-6. To eliminate our reliance on these experiments, here we use ab initio quantum chromodynamics (QCD) and quantum electrodynamics simulations to compute the LO-HVP contribution. We reach sufficient precision to discriminate between the measurement of the anomalous magnetic moment of the muon and the predictions of dispersive methods. Our result favours the experimentally measured value over those obtained using the dispersion relation. Moreover, the methods used and developed in this work will enable further increased precision as more powerful computers become available.

Lattice Computation of the Nucleon Scalar Quark Contents at the Physical Point.

We present a QCD calculation of the u, d, and s scalar quark contents of nucleons based on 47 lattice ensembles with N_{f}=2+1 dynamical sea quarks, 5 lattice spacings down to 0.054 fm, lattice sizes up to 6 fm, and pion masses down to 120 MeV. Using the Feynman-Hellmann theorem, we obtain f_{ud}^{N}=0.0405(40)(35) and f_{s}^{N}=0.113(45)(40), which translates into σ_{πN}=38(3)(3) MeV, σ_{sN}=105(41)(37) MeV, and y_{N}=0.20(8)(8) for the sigma terms and the related ratio, where the first errors are statistical and the second errors are systematic. Using isospin relations, we also compute the individual up and down quark contents of the proton and neutron (results in the main text).

Crystallization of zirconia based thin films.

The crystallization kinetics of amorphous 3 and 8 mol% yttria stabilized zirconia (3YSZ and 8YSZ) thin films grown by pulsed laser deposition (PLD), spray pyrolysis and dc-magnetron sputtering are explored. The deposited films were heat treated up to 1000 °C ex situ and in situ in an X-ray diffractometer. A minimum temperature of 275 °C was determined at which as-deposited amorphous PLD grown 3YSZ films fully crystallize within five hours. Above 325 °C these films transform nearly instantaneously with a high degree of micro-strain when crystallized below 500 °C. In these films the t'' phase crystallizes which transforms at T > 600 °C to the t' phase upon relaxation of the micro-strain. Furthermore, the crystallization of 8YSZ thin films grown by PLD, spray pyrolysis and dc-sputtering are characterized by in situ XRD measurements. At a constant heating rate of 2.4 K min(-1) crystallization is accomplished after reaching 800 °C, while PLD grown thin films were completely crystallized already at ca. 300 °C.

Multiferroic properties of o-LuMnO3 controlled by b-axis strain.

Strain is a leading candidate for controlling magnetoelectric coupling in multiferroics. Here, we use x-ray diffraction to study the coupling between magnetic order and structural distortion in epitaxial films of the orthorhombic (o-) perovskite LuMnO(3). An antiferromagnetic spin canting in the E-type magnetic structure is shown to be related to the ferroelectrically induced structural distortion and to a change in the magnetic propagation vector. By comparing films of different orientations and thicknesses, these quantities are found to be controlled by b-axis strain. It is shown that compressive strain destabilizes the commensurate E-type structure and reduces its accompanying ferroelectric distortion.

Growth of Li x La y Sr z MnO3 thin films by pulsed laser deposition: complex relation between thin film composition and deposition parameters.

Li x La y Sr z MnO3 thin films of various compositions (x,y,z) have been grown using pulsed laser deposition. The compositions of the films have been studied as a function of deposition temperature, target-to-substrate distance and deposition pressure with respect to different cation ratios of the targets by inductively coupled plasma mass spectrometry. When growing multi-elemental oxide thin films containing lithium (with its large mass difference to other elements), lithium loss is most probably inevitable. But the desired thin film composition can be achieved by selecting specific growth conditions and different target compositions. The experiments also elucidate some of the mechanisms behind the incongruent lithium transfer from the targets to thin films.

Rolling dopant and strain in Y-doped BiFeO3 epitaxial thin films for photoelectrochemical water splitting.

We report significant photoelectrochemical activity of Y-doped BiFeO3 (Y-BFO) epitaxial thin films deposited on Nb:SrTiO3 substrates. The Y-BFO photoanodes exhibit a strong dependence of the photocurrent values on the thickness of the films, and implicitly on the induced epitaxial strain. The peculiar crystalline structure of the Y-BFO thin films and the structural changes after the PEC experiments have been revealed by high resolution X-ray diffraction and transmission electron microscopy investigations. The crystalline coherence breaking due to the small ionic radius Y-addition was analyzed using Willliamson-Hall approach on the 2θ-ω scans of the symmetric (00 l) reflections and confirmed by high resolution TEM (HR-TEM) analysis. In the thinnest sample the lateral coherence length (L∥) is preserved on larger nanoregions/nanodomains. For higher thickness values L∥ is decreasing while domains tilt angles (αtilt) is increasing. The photocurrent value obtained for the thinnest sample was as high as Jph = 0.72 mA/cm2, at 1.4 V(vs. RHE). The potentiostatic scans of the Y-BFO photoanodes show the stability of photoresponse, irrespective of the film's thickness. There is no clear cathodic photocurrent observation for the Y-BFO thin films confirming the n-type semiconductor behavior of the Y-BFO photoelectrodes.

Urinary phytoestrogen excretion of rats bearing methylnitrosourea-induced mammary carcinoma in response to treatment with 2-methoxyestradiol.

The effect of treating mammary tumor-bearing rats with 2-methoxyestradiol (2-MeE2) on the urinary excretion of 12 phytoestrogens was investigated and compared with the changes in urinary excretion of estradiol metabolites. Alterations of excretion were registered for isoflavonoids, lignans and coumestans. However, due to large variations statistical significant differences were found only for two lignans, i.e. significant increases of enterodiol and matairesinol. Since the single components of phytoestrogens showed diverse alterations, excretions were expressed also by the ratio of total isoflavonoids to total lignans and compared with the estrogen ratios 2-hydroxyestrone to 16alpha-hydroxyestrone and A-ring to D-ring metabolites. The ratio of isoflavonoids to lignans was consistently decreased, whereas both ratios of estradiol metabolites were highly increased. The latter effect is probably due to demethylation of 2-methoxyestrone resulting in high catechol estrogen levels in urine. These results suggest that the high levels of catechol estrogens, produced by 2-MeE2 treatment, may have influenced the urinary excretion pattern of phytoestrogens.

Ab initio calculation of the neutron-proton mass difference.

The existence and stability of atoms rely on the fact that neutrons are more massive than protons. The measured mass difference is only 0.14% of the average of the two masses. A slightly smaller or larger value would have led to a dramatically different universe. Here, we show that this difference results from the competition between electromagnetic and mass isospin breaking effects. We performed lattice quantum-chromodynamics and quantum-electrodynamics computations with four nondegenerate Wilson fermion flavors and computed the neutron-proton mass-splitting with an accuracy of 300 kilo-electron volts, which is greater than 0 by 5 standard deviations. We also determine the splittings in the Σ, Ξ, D, and Ξcc isospin multiplets, exceeding in some cases the precision of experimental measurements.

Effect of 2-methoxyestradiol on the growth of methyl-nitroso-urea (MNU)-induced rat mammary carcinoma.

The present study investigated the influence of the endogenous estradiol metabolite 2-methoxyestradiol (2ME) on the growth of methyl-nitroso-urea (MNU)-induced mammary carcinoma in the rat. 2ME was administered by means of subcutaneously implanted osmotic pumps for a period of 4 weeks. The dosages of 2ME were 1 and 5mg/kg per day, the control animals received saline. At the low dosage of 2ME a stimulation of tumor growth was observed, whereas at the high dosage an inhibition was found. The urinary excretion of 15 estradiol metabolites revealed that 2ME triggered strong changes in estrogen metabolism in the organism. Our data show that 2ME may elicit both stimulation and inhibition of tumor growth depending on the dosage used, a fact which should be considered in case of therapeutic use.

The effect of zearalenone and 17 beta-estradiol on prostacyclin and thromboxane production in cell cultures from human umbilical cord veins.

The effect of zearalenone, a nonsteroidal mycotoxin with estrogenic activity, and of 17 beta-estradiol on prostacyclin and thromboxane production in human endothelial cells was investigated. Zearalenone stimulated prostacyclin production in low concentrations (10(-7) and 10(-8)M) and inhibited it at a higher concentration (10(-5)M). Estradiol alone in the concentration range 10(-5)-10(-8)M had no clear-cut effect on the prostacyclin production. The combination of both substances effected changes in prostacyclin production similar to that from zearalenone alone; with the exception of estradiol at a concentration of 10(-6)M which enhanced the effect of zearalenone. No distinct changes in the thromboxane production from the two substances could be found, either alone or in combination.

Immunoreactive ubiquitin in human seminal plasma.

The polypeptide ubiquitin, up to now almost exclusively discovered in intracellular spaces, was measured immunologically in a total of 187 samples of human seminal plasma. The values were between 1.83 and 19.11 micrograms/ml. In spermatozoa ubiquitin was detected too; the values, however, were significantly lower than in the seminal plasma. The origin and function of ubiquitin in human seminal plasma is still unclear. The possible role of ubiquitin in reproduction is discussed.

Effect of estradiol metabolites on prostacyclin synthesis in human endothelial cell cultures.

Estradiol can stimulate prostacyclin production in the vessel wall, thereby eliciting vasodilatation. In the present work the effect of the estradiol metabolites estrone, 2-methoxyestrone, 2-methoxyestradiol, and 16alpha-hydroxyestrone were investigated to find out if they are also able to stimulate prostacyclin synthesis. All metabolites triggered an increase of prostacyclin synthesis in human endothelial cells starting at a concentration of 10(-9) M. The parent substance, 17beta-estradiol, accomplished this effect only starting at a concentration of 10(-8) M. These results indicate that estradiol metabolites may take part in the estradiol-induced vasodilatation in vivo.

Effect of estradiol metabolites on the susceptibility of low density lipoprotein to oxidation.

The main estradiol metabolites 2-hydroxyestrone, 2-methoxyestrone and 16alpha-hydroxyestrone were investigated in vitro for the susceptibility of low density lipoprotein to oxidation and the effects compared with those of estradiol and vitamin E. 2-hydroxyestrone and 2-methoxyestrone had a greater inhibitory effect than estradiol and vitamin E whereas 16alpha-hydroxyestrone approximates the inhibition of estradiol. These results indicate that 2-hydroxyestrone and 2-methoxyestrone possess non-genomic actions which may play a role in the lipid metabolism.

The effects of A-ring and D-ring metabolites of estradiol on the proliferation of vascular endothelial cells.

The effects of 14 estradiol metabolites on the proliferation of cultured endothelial cells of human umbilical cord veins were examined and compared with that of their parent substance estradiol. The relationship between dosage and effect was tested over the pharmacological concentration range of 10(-8) to 10(-5) M. Estradiol showed a biphasic behaviour, in the form of stimulation at low concentrations and inhibition at the highest concentration. All 10 A-ring metabolites tested stimulated the growth of the endothelial cells at the lower concentrations. At the highest concentration, the 5 A-ring metabolites: 2-hydroxyestrone, 2-hydroxyestradiol, 2-hydroxyestriol, 4-hydroxyestrone and 4-hydroxyestradiol caused significant inhibitions. Except for the 2-hydroxyestradiol, methylation of these metabolites resulted in the loss of the proliferation inhibiting effect. The D-ring metabolites showed no marked effects compared to the A-ring metabolites except for 16alpha-hydroxyestrone which had an inhibiting effect from 10(-7) to 10(-5) M. Our results show that estradiol metabolites can influence the growth of vascular endothelial cells in the concentration range tested. While the antiproliferative action of 2-methoxyestradiol has been known for some time this study is the first to show the potential capacity of non-methylated metabolites of the A-ring metabolism in inhibiting endothelial proliferation. This may open up new clinical pharmacological aspects in the anti-angiogenetic treatment of tumors.

The impact of endogenous estradiol metabolites on carcinogenesis.

The available literature on estrogen metabolism and estrogen metabolites involved in carcinogenesis is reviewed. Endogenous estradiol metabolism leads to metabolic products that can have various, and, to some extent, contrary, biologic effects. Thus, there are numerous research findings on the stimulation and inhibition of cancer growth by estrogen metabolites. Furthermore, there are indications that, in certain types of cancer, the production of growth-stimulating estradiol metabolites is increased. There are also reports on substances that can influence estradiol metabolism. So far, only a few estradiol metabolites have been examined with respect to their influence on the development and growth of cancer. It is presumed that other metabolites can also intervene directly or indirectly in the cancer process, but there is a great lack of research in this area. An understanding of the actions of estradiol metabolites may open up new avenues for the therapy of malignant diseases. Although little is known about the biologic effects of most of the estradiol metabolites, the reported actions of certain estradiol metabolites already justify clinical investigations on their possible beneficial uses in tumor therapy.

Urinary cGMP excretion after hormone replacement therapy in postmenopausal women.

It is well established that estrogens and progestogens are able to influence the vasotonus in postmenopausal women. The present study was undertaken to find out if the NO/cGMP-system is involved in this hormone action. Urinary cGMP excretion which can reflect intracellular cGMP production elicited by NO (EDRF) was investigated in 20 postmenopausal women. In an open cross-over study design norethisterone acetate was administered orally for 8 days, estradiol valerate orally for 9 days and a combination of both substances for 12 days. After all three treatment phases urinary cGMP expressed as percentage of the pretreatment value was increased at a statistically significant level. Due to high individual variations no significant differences could be found among the values after the three treatment phases. It was concluded that the NO/cGMP-system may play a role in maintaining vasotonus in postmenopausal women under hormone replacement therapy.

Effects of valsartan and 17 beta-estradiol on the oxidation of low-density lipoprotein in vitro.

BACKGROUND: The 'sartans' are antagonists of the angiotensin type 1 (AT1) receptor that are mainly used for treatment of hypertension. Little is known about AT1-independent effects of these substances and interactions with other drugs used for prevention of cardiovascular diseases. Postmenopausal estradiol-replacement therapy has been shown to exert beneficial antiathero-sclerotic properties by inhibiting oxidation of low-density lipoprotein (LDL). OBJECTIVE: In the present study, the effects of valsartan alone and in combination with 17 beta-estradiol on the oxidation of isolated human LDL were investigated. METHODS: Oxidation of LDL, which was triggered by copper (II) chloride, was monitored spectrometrically at 234 nm. The test substances were added in vitro. RESULTS: Valsartan alone increased the duration of resistance of LDL to oxidation by 75.3 +/- 5.7 min at 5 mumol/l and by 138.2 +/- 8.1 min at 10 mumol/l. 17 beta-estradiol alone delayed the onset of oxidation of LDL by 75.7 +/- 5.1 min at 1 mumol/l. With the combination of 5 and 10 mumol/l valsartan with 1 mumol/l estradiol the time to onset of oxidation of LDL was increased by 142.8 +/- 4.9 and 215.3 +/- 6.9 min, respectively. CONCLUSIONS: There has been demonstrated an antioxidative effect of valsartan that was additive to that of 17 beta-estradiol. Thus this combination has the potential to be useful in the treatment of postmenopausal women with hypertension.

Serotonin metabolite excretion after postmenopausal estradiol therapy.

Serotonin, known for its beneficial action on mood and well-being, is also involved in cardiovascular functions. Thus the current work was undertaken to study the effect of hormone replacement therapy on serotonin turnover in postmenopausal women. Eighteen women received estradiol transdermally and 17 women estradiol valerate orally for 4 weeks. The serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) was determined in the urine before, and after 2 and 4 weeks' estradiol treatment. With both administration routes estradiol produced a significant increase in urinary 5-HIAA excretion, greatest with transdermal estradiol after 28 days of treatment. The enhancement of serotonin turnover may contribute not only to an improvement of mood and well-being but also to a cardioprotective effect of estradiol observed after hormone substitution in postmenopausal women.

Continuous-combined treatment of the menopause with combinations of oestradiol valerate and dienogest - a dose-ranging study.

OBJECTIVES: To determine the progestational efficacy of continuous treatment with various doses of dienogest, combined with oestradiol valerate, on the basis of endometrial histology, effect on climacteric symptoms and bleeding profile in postmenopausal women. METHODS: Patients were randomised to one of five fixed-combination treatments, oestradiol valerate 2.0 mg plus dienogest 0.5, 1.0, 2.0, 3.0 or 4.0 mg. Efficacy was assessed by endometrial biopsy, menstrual charts and change in climacteric symptoms. RESULTS: The endometrium was classified as atrophic in 20.0, 31.3, 25.0, 55.6 and 57.1% of patients in the 0.5, 1.0, 2.0, 3.0 and 4.0 mg dienogest groups, respectively. The frequency of uterine bleeding was dose-dependent. The most favourable bleeding profile was seen in the 3.0 mg dienogest group, whereas the lower doses of dienogest had advantages with respect to the efficacy of the combined preparation. CONCLUSIONS: Dienogest 2.0 and 3.0 mg are the optimal doses for combination with 2.0 mg oestradiol valerate for continuous-combined hormone replacement therapy.

Effect of 17 alpha-ethinylestradiol, levonorgestrel, 3-keto-desogestrel, and gestodene on calcium influx via voltage-gated calcium channels in human aortic smooth muscles.

The effect of the synthetic estradiol, 17 alpha-ethinylestradiol, and three progestogens on calcium influx was investigated in cell cultures of human aortic smooth muscle. Neither the synthetic estrogen nor the progestogens levonorgestrel, 3-keto-desogestrel, and gestodene showed, in the concentration range of 10(-9) to 10(-6) M, a significant effect on calcium influx both alone or in equimolar estrogen-gestagen combinations. The results indicate that these substances, commonly used in contraceptive pills, do not change vasotonus interfering with calcium homeostasis.