641 research outputs found
An adequate logic for full LOTOS
We present a novel result for a logic for symbolic transition systems based on LOTOS processes. The logic is adequate with respect to bisimulation defined on symbolic transition systems
Participation, Mutation and Political Transition: New Democratic Spaces in Peri-Urban Angola
This chapter examines participation spaces in peri-urban Luanda, Angola – a context very different from those that have originated most recent studies in this field and which presents a series of apparently highly adverse conditions for the development of citizen participation. Sometimes labelled a ‘fragile ’ or ‘failed ’ state, Angola coul
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The principles underlying the use of powder diffraction data in solving pharmaceutical crystal structures
Solving pharmaceutical crystal structures from powder diffraction data is discussed in terms of the methodologies that have been applied and the complexity of the structures that have been solved. The principles underlying these methodologies are summarized and representative examples of polymorph, solvate, salt and cocrystal structure solutions are provided, together with examples of some particularly challenging structure determinations
On the Method to Infer an Atmosphere on a Tidally-Locked Super Earth Exoplanet and Upper limits to GJ 876d
We develop a method to infer or rule out the presence of an atmosphere on a
tidally-locked hot super Earth. The question of atmosphere retention is a
fundamental one, especially for planets orbiting M stars due to the star's
long-duration active phase and corresponding potential for stellar-induced
planetary atmospheric escape and erosion. Tidally-locked planets with no
atmosphere are expected to show a Lambertian-like thermal phase curve, causing
the combined light of the planet-star system to vary with planet orbital phase.
We report Spitzer 8 micron IRAC observations of GJ 876 taken over 32
continuous hours and reaching a relative photometric precision of 3.9e-04 per
point for 25.6 s time sampling. This translates to a 3 sigma limit of 5.13e-05
on a planet thermal phase curve amplitude. Despite the almost photon-noise
limited data, we are unable to conclusively infer the presence of an atmosphere
or rule one out on the non-transiting short-period super Earth GJ 876d. The
limiting factor in our observations was the miniscule, monotonic photometric
variation of the slightly active host M star, because the partial sine wave due
to the planet has a component in common with the stellar linear trend. The
proposed method is nevertheless very promising for transiting hot super Earths
with the James Webb Space Telescope and is critical for establishing
observational constraints for atmospheric escape.Comment: Published in Ap
Elucidating an amorphous form stabilization mechanism of tenapanor hydrochloride: crystal structure analysis using Xray diffraction, NMR crystallography and molecular modelling
By the combined use of powder and single crystal X-ray diffraction, solid-state NMR, and molecular modelling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) assisted solid-state NMR (SSNMR) crystallography investigations were found essential for the final assignment, and were used to validate the crystal structure of ANHY. From the structural informatics analysis of ANHY and 2HCl, conformational ring differences in one part of the molecule were observed which influences the relative orientation of a methyl group on a ring nitrogen and thereby impacts the crystallizability of the dihydrochloride salt. From quantum chemistry calculations, the dynamics between different ring conformations in tenapanor is predicted to be fast. Addition of HCl to tenapanor results in general in a mixture of protonated ring conformers and hence a statistical mix of diastereoisomers which builds up the amorphous form, a-2HCl. This was qualitatively verified by 13C CP/MAS NMR investigations of the amorphous form. Thus, to form any significant amount of the crystalline material 2HCl, which originates from the minor (i.e., energetically less stable) ring conformations, one needs to involve nitrogen deprotonation to allow exchange between minor and major conformations of ANHY in solution. Thus, by controlling the solution pH value to well below the pKa of ANHY, the equilibrium between ANHY and 2HCl can be controlled and by this mechanism the crystallization of 2HCl can be avoided and the amorphous form of the dichloride salt can therefore be stabilized
The quetiapine active metabolite N-Desalkylquetiapine and the neurotensin NTS1 receptor agonist PD149163 exhibit antidepressant-like effects on operant responding in male rats
Major depressive disorder (MDD) is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that are apparent following one week of quetiapine treatment, and it is possible that the active metabolite N-Desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS1 receptor agonist PD149163 are suggestive of antidepressant efficacy, but the effects of a NTS1 receptor agonist in an antidepressant animal model have yet to be reported. The present study examined the antidepressant-like effects of the N-Desalkylquetiapine, the neurotensin NTS1 receptor agonist PD14916, quetiapine, the tricylic antidepressant drug imipramine, the atypical antipsychotic drug risperidone, and the typical antipsychotic drug raclopride on responding in male Sprague-Dawley rats trained on a differential-reinforcement-of-low-rate (DRL) 72 s operant schedule, a procedure used for screening antidepressant drugs. Quetiapine, PD149163, risperidone, and imipramine exhibited antidepressant-like effects by increasing the number of reinforcers earned, decreasing the number of responses emitted, and shifting the interresponse time (IRT) distributions to the right. N-Desalkylquetiapine produced a partial antidepressant-like effect by decreasing the number of responses emitted and producing a rightward shift in the IRT distributions, but it did not significantly alter the number of reinforcers earned. The typical antipsychotic drug raclopride decreased both reinforcers and responses. These data suggest that N-Desalklyquetiapine likely contributes to quetiapine’s antidepressant efficacy and identifies NTS1 receptor activation as a potential novel pharmacologic strategy for antidepressant drugs
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Asymmetric cyclopropanation of conjugated cyanosulfones using a novel cupreine organocatalyst: rapid access to d3-amino acids
An organocatalytic asymmetric synthesis of a novel, highly functionalised cyclopropane system furnished with versatile substituents and containing a quaternary centre is described. The process utilises a new bifunctional catalyst based on the cinchona alkaloid framework and the products made using this catalyst were obtained as single diastereoisomers, with very high enantioselectivities (up to 96% ee). We have also demonstrated that these resulting cyclopropanes are very useful synthetic intermediates to interesting products, such as the difficult to access d3-amino acids
Arago (1810): the first experimental result against the ether
95 years before Special Relativity was born, Arago attempted to detect the
absolute motion of the Earth by measuring the deflection of starlight passing
through a prism fixed to the Earth. The null result of this experiment gave
rise to the Fresnel's hypothesis of an ether partly dragged by a moving
substance. In the context of Einstein's Relativity, the sole frame which is
privileged in Arago's experiment is the proper frame of the prism, and the null
result only says that Snell's law is valid in that frame. We revisit the
history of this premature first evidence against the ether theory and calculate
the Fresnel's dragging coefficient by applying the Huygens' construction in the
frame of the prism. We expose the dissimilar treatment received by the ray and
the wave front as an unavoidable consequence of the classical notions of space
and time.Comment: 16 pages. To appear in European Journal of Physic
p35, the non-cyclin activator of Cdk5, protects podocytes against apoptosis in vitro and in vivo
Cyclin-dependent kinase-5 is widely expressed and predominantly regulated by the non-cyclin activator p35. Since we recently showed that expression of p35 in the kidney is restricted to podocytes, we examined here its function in mice in which p35 was genetically deleted. The mice did not exhibit kidney abnormalities during glomerular development or during adult life. Conditionally immortalized cultured podocytes, derived from these null mice, did not have any change in their morphology, differentiation, or proliferation. However, when these cultured podocytes were exposed to UV-C irradiation, serum depletion, puromycin aminonucleoside, or transforming growth factor-β-1, they showed increased apoptosis compared to those from wild-type mice. Levels of Bcl-2 were decreased in these null podocytes but increased after transduction with human p35. Restoration of p35 or the ectopic expression of Bcl-2 reduced the susceptibility of p35-null podocytes to apoptosis. Experimental glomerulonephritis, characterized by podocyte apoptosis and subsequent crescent formation, was utilized to test these findings in vivo. Podocyte apoptosis was significantly increased in diseased p35-null compared with wild-type mice, accompanied by increased glomerulosclerosis and decreased renal function. Our study shows that p35 does not affect glomerulogenesis but controls podocyte survival following injury, in part, by regulating Bcl-2 expression
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