18 research outputs found

    Nonlocal Astroparticles in Einstein's Universe

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    Gravitational probes should maintain spatial flatness for Einsten-Infeld-Hoffmann dynamics of relativistic matter-energy. The continuous elementary source/particle in Einstein's gravitational theory is the r^{-4} radial energy density rather than the delta-operator density in empty-space gravitation. The space energy integral of such an infinite (astro)particle is finite and determines its nonlocal gravitational charge for the energy-to-energy attraction of other nonlocal (astro)particles. The non-empty flat space of the undivided material Universe is charged continuously by the world energy density of the global ensemble of overlapping radial particles. Nonlocal gravitational/inertial energy-charges incorporate Machian relativism quantitatively into Einstein's gravitation for self-contained SR-GR dynamics without references on Newton's mass-to-mass attraction.Comment: 9 pages, typos and arguments adde

    Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

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    Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

    Phenomenology of the Lense-Thirring effect in the Solar System

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    Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

    Gravitational experiments in space: Gravity probe B and STEP

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    We describe two space based gravitational physics experiments, the Gravity Probe B Relativity Mission (GPB) and the Satellite Test of the Equivalence Principle (STEP). GP-B will perform precision tests of two independent predictions of general relativity, the geodetic effect and frame dragging. STEP will provide a precision test of a foundation of general relativity, the Equivalence Principle

    Preprint: Structural requirements for dihydrobenzoxazepinone anthelmintics: actions against medically important and model parasites - Trichuris muris, Brugia malayi, Heligmosomoides polygyrus and Schistosoma mansoni

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    Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from Trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority, and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesised 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action, as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQ) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics
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