1,999 research outputs found

    Mechanisms Of Fracturing In Structures Built From Topologically Interlocked Blocks

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    Failure of materials is in many cases associated with initiation and subsequent propagation of macroscopic fractures. Consequently, in order to increase the strength, one needs to inhibit either crack initiation or propagation. The principle of topological interlocking provides a unique opportunity to construct materials and structures in which both routes of the strength increase can be realised. Materials and structures built on the basis of this principle consist of many elements which are hold together by the special geometry of their shape, together with an external constrain. The absence of the binder phase between the elements allows the interfaces to arrest macroscopic crack propagation. In addition, with sufficiently small size of the elements an increase in local strength and, possibly, in the stress for crack initiation can be achieved by capitalising on the size effect. Furthermore, the ability of some interlocking structures to tolerate missing elements can serve to prevent the avalanche-type failure initiated by failure of one of the elements. In this paper, experimental results and a theoretical analysis with regard to this possibility are presented

    7‑hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects

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    Mitragynina speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine, and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.</p

    A holomorphic representation of the Jacobi algebra

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    A representation of the Jacobi algebra h1⋊su(1,1)\mathfrak{h}_1\rtimes \mathfrak{su}(1,1) by first order differential operators with polynomial coefficients on the manifold C×D1\mathbb{C}\times \mathcal{D}_1 is presented. The Hilbert space of holomorphic functions on which the holomorphic first order differential operators with polynomials coefficients act is constructed.Comment: 34 pages, corrected typos in accord with the printed version and the Errata in Rev. Math. Phys. Vol. 24, No. 10 (2012) 1292001 (2 pages) DOI: 10.1142/S0129055X12920018, references update

    Accelerator system for the PRISM based muon to electron conversion experiment

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    The next generation of lepton flavor violation experiments need high intensity and high quality muon beams. Production of such beams requires sending a short, high intensity proton pulse to the pion production target, capturing pions and collecting the resulting muons in the large acceptance transport system. The substantial increase of beam quality can be obtained by applying the RF phase rotation on the muon beam in the dedicated FFAG ring, which was proposed for the PRISM project.This allows to reduce the momentum spread of the beam and to purify from the unwanted components like pions or secondary protons. A PRISM Task Force is addressing the accelerator and detector issues that need to be solved in order to realize the PRISM experiment. The parameters of the required proton beam, the principles of the PRISM experiment and the baseline FFAG design are introduced. The spectrum of alternative designs for the PRISM FFAG ring are shown. Progress on ring main systems like injection and RF are presented. The current status of the study and its future directions are discussed.Comment: Studies performed within the PRISM Task Force initiativ

    Tin telluride: a weakly co-elastic metal

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    We report resonant ultrasound spectroscopy (RUS), dilatometry/magnetostriction, magnetotransport, magnetization, specific heat, and 119^{119}Sn M\"ossbauer spectroscopy measurements on SnTe and Sn0.995_{0.995}Cr0.005_{0.005}Te. Hall measurements at T=77T=77 K indicate that our Bridgman-grown single crystals have a pp-type carrier concentration of 3.4×10193.4 \times 10^{19} cm−3^{-3} and that our Cr-doped crystals have an nn-type concentration of 5.8×10225.8 \times 10^{22} cm−3^{-3}. Although our SnTe crystals are diamagnetic over the temperature range 2 K≤T≤1100 K2\, \text{K} \leq T \leq 1100\, \text{K}, the Cr-doped crystals are room temperature ferromagnets with a Curie temperature of 294 K. For each sample type, three-terminal capacitive dilatometry measurements detect a subtle 0.5 micron distortion at Tc≈85T_c \approx 85 K. Whereas our RUS measurements on SnTe show elastic hardening near the structural transition, pointing to co-elastic behavior, similar measurements on Sn0.995_{0.995}Cr0.005_{0.005}Te show a pronounced softening, pointing to ferroelastic behavior. Effective Debye temperature, θD\theta_D, values of SnTe obtained from 119^{119}Sn M\"ossbauer studies show a hardening of phonons in the range 60--115K (θD\theta_D = 162K) as compared with the 100--300K range (θD\theta_D = 150K). In addition, a precursor softening extending over approximately 100 K anticipates this collapse at the critical temperature, and quantitative analysis over three decades of its reduced modulus finds ΔC44/C44=A∣(T−T0)/T0∣−κ\Delta C_{44}/C_{44}=A|(T-T_0)/T_0|^{-\kappa} with κ=0.50±0.02\kappa = 0.50 \pm 0.02 , a value indicating a three-dimensional softening of phonon branches at a temperature T0∼75T_0 \sim 75 K, considerably below TcT_c. We suggest that the differences in these two types of elastic behaviors lie in the absence of elastic domain wall motion in the one case and their nucleation in the other
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