Slowly modulated oscillations in nonlinear diffusion processes

It is shown here that certain systems of nonlinear (parabolic) reaction-diffusion equations have solutions which are approximated by oscillatory functions in the form R(ξ - cτ)P(t^*) where P(t^*) represents a sinusoidal oscillation on a fast time scale t* and R(ξ - cτ) represents a slowly-varying modulating amplitude on slow space (ξ) and slow time (τ) scales. Such solutions describe phenomena in chemical reactors, chemical and biological reactions, and in other media where a stable oscillation at each point (or site) undergoes a slow amplitude change due to diffusion

Asymptotic Analysis of Buffered Calcium Diffusion near a Point Source

The domain calcium (Ca2+) concentration near an open Ca2+ channel can be mod- eled as buffered diffusion from a point source. The concentration profiles can be well approximated by hemispherically symmetric steady-state solutions to a system of reaction-diffusion equations. After nondimensionalizing these equations and scaling space so that both reaction terms and the source amplitude are 0(1), we identify two dimensionless parameters, Cc and Eb, that correspond to the diffusion coefficients of dimensionless Ca2+ and buffer, respectively. Using perturbation methods, we derive approximations for the Ca2+ and buffer profiles in three asymptotic limits: (1) an excess buffer approximation (EBA), where the mobility of buffer exceeds that of Ca2+ (Eb \u3e Ec) and the fast diffusion of buffer toward the Ca2+ channel prevents buffer saturation (cf. Neher [Calcium Electrogenesis and Neuronal Functioning, Exp. Brain Res. 14, Springer-Verlag, Berlin, 1986, pp. 80-96]); (2) a rapid buffer approximation (RBA), where the diffusive time-scale for Ca2+ and buffer are comparable, but slow compared to reaction (ec \u3c\u3c 1, Eb reaction (ec \u3c\u3c 1, Eb reaction (ec \u3c\u3c 1, E

Hypothetical membrane mechanisms in essential tremor

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An inter-laboratory comparison of standard membrane-feeding assays for evaluation of malaria transmission-blocking vaccines.

BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. While several studies have discussed the inherent variability of SMFA within a study group, there has been no assessment of inter-laboratory variation. Therefore, there is currently no assurance that SMFA results are comparable between different studies. METHODS: Mouse anti-Pfs25 monoclonal antibody (mAb, 4B7 mAb), rat anti-Pfs48/45 mAb (85RF45.1 mAb) and a human polyclonal antibody (pAb) collected from a malaria-exposed adult were tested at the same concentrations (6-94 μg/mL for 4B7, 1.2-31.3 μg/mL for 85RF45.1 and 23-630 μg/mL for human pAb) in two laboratories following their own standardized SMFA protocols. The mAbs and pAb, previously shown to have strong inhibition activities in the SMFA, were tested at three or four concentrations in two or three independent assays in each laboratory, and percent inhibition in mean oocyst intensity relative to a control in the same feed was determined in each feeding experiment. RESULTS: Both monoclonal and polyclonal antibodies dose-dependently reduced oocyst intensity in all experiments performed at the two test sites. In both laboratories, the inter-assay variability in percent inhibition in oocyst intensity decreased at higher levels of inhibition, regardless of which antibody was tested. At antibody concentrations that led to a >80 % reduction in oocyst numbers, the inter-laboratory variations were in the same range compared with the inter-assay variation observed within a single laboratory, and the differences in best estimates from multiple feeds between the two laboratories were <5 percentage points. CONCLUSIONS: This study confirms previous reports that the precision of the SMFA increases with increasing percent inhibition. Moreover, the variation between the two laboratories is not greater than the variation observed within a laboratory. The findings of this study provide guidance for comparison of SMFA data from different laboratories

Vortices in (2+1)d Conformal Fluids

We study isolated, stationary, axially symmetric vortex solutions in (2+1)-dimensional viscous conformal fluids. The equations describing them can be brought to the form of three coupled first order ODEs for the radial and rotational velocities and the temperature. They have a rich space of solutions characterized by the radial energy and angular momentum fluxes. We do a detailed study of the phases in the one-parameter family of solutions with no energy flux. This parameter is the product of the asymptotic vorticity and temperature. When it is large, the radial fluid velocity reaches the speed of light at a finite inner radius. When it is below a critical value, the velocity is everywhere bounded, but at the origin there is a discontinuity. We comment on turbulence, potential gravity duals, non-viscous limits and non-relativistic limits.Comment: 39 pages, 10 eps figures, v2: Minor changes, refs, preprint numbe

Comparative assessment of An. gambiae and An. stephensi mosquitoes to determine transmission-reducing activity of antibodies against P. falciparum sexual stage antigens.

BACKGROUND: With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa. METHODS: Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An. stephensi and An. gambiae mosquitoes. RESULTS: In the absence of transmission-reducing antibodies, average numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody-mediated TRA was strongly correlated between both mosquito species, and absolute TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no significant difference between the two species. TRA estimates for IgG of naturally exposed individuals and partially effective concentrations of anti-Pfs25 mAb were higher for An. stephensi than for An. gambiae. CONCLUSION: Our findings support the use of An. stephensi in the SMFA for target prioritization. As a vaccine moves through product development, better estimates of TRA and transmission-blocking activity (TBA) may need to be obtained in epidemiologically relevant parasite-species combination

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

DNA methylation patterns of Brachypodium distachyon chromosomes and their alteration by 5-azacytidine treatment

Sequential immunolocalisation of 5-methylcytosine (5-MeC) and fluorescence in situ hybridisation with chromosome-specific BAC clones were performed on Brachypodium distachyon mitotic metaphase chromosomes to determine specific DNA methylation patterns of each chromosome in the complement. In the majority of cells examined, chromosomes Bd4 and Bd5, which bear the loci of 5S and 35S ribosomal DNA, respectively, had characteristic 5-MeC patterns. In contrast, the distribution of 5-MeC along the metacentric chromosome pairs Bd1, Bd2 and Bd3 was more variable. There were numerous differences in distribution of methylated sites between homologous chromosomes as well as between chromosome arms. Some chromosome sites, such as pericentromeric regions, were highly methylated in all chromosomes. Additionally, the influence of a hypomethylating agent, 5-azacytidine, on B. distachyon chromosome methylation patterns was confirmed. It was found that some chromosome pairs underwent demethylation more easily than others, but there was no apparent regularity in demethylation of particular chromosome segments