Abstract. Progeny of Aedes aegypti mosquitoes infected intrathoracically with dengue-3 virus was reared to subsequent generations. In each generation, blood-fed females were confined individually and the eggs obtained from the transovarially infected females were pooled. The seventh generation obtained from the infected parental mosquitoes showed that virus could persist in mosquitoes in successive generations through transovarial passage. The rate of vertical transmission initially increased in the few generations (F 1 -F 2 ), but in subsequent generations it was found to be steady. Parental mosquitoes inoculated with virus showed higher mortality than the diluent-inoculated controls. There was an increase in the larval duration of transovarially infected batches at the seventh generation when compared with uninfected control mosquitoes. The fecundity and fertility of the transovarially infected batches of mosquitoes was also affected when compared with the controls. This is the first report demonstrating persistence of dengue virus in the successive generations of mosquitoes infected through vertical transmission. These observations, which have great epidemiologic importance, suggest that vector mosquitoes may play an important role in the maintenance of virus in nature, and that mosquitoes may act as reservoirs of these viruses.

We present a positivity preserving variational scheme for the phase-field modeling of incompressible two-phase flows with high density ratio and using meshes of arbitrary topology. The variational finite element technique relies on the Allen-Cahn phase-field equation for capturing the phase interface on a fixed mesh with a mass conservative and energy-stable discretization. Mass is conserved by enforcing a Lagrange multiplier which has both temporal and spatial dependence on the solution of the phase-field equation. The spatial part of the Lagrange multiplier is written as a mid-point approximation to make the scheme energy-stable. This enables us to form a conservative, energy-stable and positivity preserving scheme. The proposed variational technique reduces spurious and unphysical oscillations in the solution while maintaining second-order spatial accuracy. To model a generic two-phase free-surface flow, we couple the Allen-Cahn phase-field equation with the Navier-Stokes equations. Comparison of results between standard linear stabilized finite element method and the present variational formulation shows a remarkable reduction of oscillations in the solution while retaining the boundedness of the phase-indicator field. We perform a standalone test to verify the accuracy and stability of the Allen-Cahn two-phase solver. Standard two-phase flow benchmarks such as Laplace-Young law and sloshing tank problem are carried out to assess the convergence and accuracy of the coupled Navier-Stokes and Allen-Cahn solver. Two-and three-dimensional dam break problem are then solved to assess the scheme for the problem with topological changes of the air-water interface on unstructured meshes. Finally, we demonstrate the phase-field solver for a practical problem of wavestructure interaction in offshore engineering using general three-dimensional unstructured meshes.

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A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride, (1), was isolated from Prosopis glandulosa Torr. var. glandulosa. Three additional new (2-4) and one known (5), indolizidines were also isolated, and the dihydrochloride salts of 1-3 (compounds 6, 7 and 8) were prepared. Structures were determined by 1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal activity against Cryptococcus neoformans and Aspergillus fumigatus (IC 50 values = 0.4 and 3.0 μg/mL, respectively), and antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare (IC 50 values of 0.35 and 0.9 μg/mL, respectively). The remarkable in vitro fungicidal activity of 1-4 against C. neoformans (MFCs = 0.63→1.25 μg/mL) and 2, 3, and 5 against A. fumigatus (MFCs = 0.63→2.5 μg/mL) were similar to amphotericin B, but >2-4-fold more potent than 6-8. Prosopilosidine (1) showed potent in vivo activity at 0.0625 mg/Kg/day/ip for 5 days in a murine model of cryptococcosis by eliminating ~76% of C. neoformans infection from brain tissue compared to ~83% with amphotericin B at 1.5 mg/Kg/day. Compounds 1 and 4 exhibited potent activity and high selectivity index (SI) values against chloroquine sensitive (D6) and chloroquine resistant (W2) strains of Plasmodium falciparum with IC 50 values of 39 and 95 ng/mL, and 42 and 120 ng/mL, respectively; (chloroquine, IC 50 = 17 and 140 ng/mL). Prosopilosine (1) also showed in vivo antimalarial activity with an ED 50 value of ~2 mg/Kg/day/ip against Plasmodium bergheiinfected mice after 3 days of treatment.Plants of the genus Prosopis are trees or shrubs distributed in arid and semiarid tropical and subtropical regions. P. glandulosa Torrey var. glandulosa (Leguminosae), a medium-sized * To whom correspondence should be addressed. Tel. (662) Decoctions of leaves and pods are generally used to make eye washes to treat pink eye. 5 An ethanolic extract of P. glandulosa from Pakistan yielded triterpenes, flavonoids, glycosides and the indolizidine alkaloid juliprosopine. [6][7][8][9][10] Among the indolizidines reported from Prosopis species to date, 6-11 the stereochemistry of juliprosine and juliprosopine were established by chemical synthesis. 12 The piperidinyl indolizidines, such as juliprosopine, and their analogs exhibited in vitro antibmicrobial, antidermatophytic, pesticidal, and amebicidal activities. 11,[13][14][15][16][17][18][19][20] In addition, their toxicity, 20-22 DNA binding activity 23 , inhibitory effects on β-glucosidase enzymes 23 and plant growth inhibitory activities were also reported. 10,24 This paper describes the isolation of the new potent antifungal and antimalarial dihydroindolizinium chloride prosopilosidine (1) from honey mesquite, together with three new analogs prosopilosine (2), isoprosopilosine (3) and isoprosopilosidine (4), and the known juliprosopine (5). 25,26 P. glandulosa Torrey var. glandulosa, has not previously been subjected to chemical or biological investigations. Prosop...

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