Liesegang patterns: Effect of dissociation of the invading electrolyte

The effect of dissociation of the invading electrolyte on the formation of Liesegang bands is investigated. We find, using organic compounds with known dissociation constants, that the spacing coefficient, 1+p, that characterizes the position of the n-th band as x_n ~ (1+p)^n, decreases with increasing dissociation constant, K_d. Theoretical arguments are developed to explain these experimental findings and to calculate explicitly the K_d dependence of 1+p.Comment: RevTex, 8 pages, 3 eps figure

Teratogenic risk and contraceptive counselling in psychiatric practice: analysis of anticonvulsant therapy

<p>Background: Anticonvulsants have been used to manage psychiatric conditions for over 50 years. It is recognised that some, particularly valproate, carbamazepine and lamotrigine, are human teratogens, while others including topiramate require further investigation. We aimed to appraise the documentation of this risk by psychiatrists and review discussion around contraceptive issues.</p> <p>Methods: A retrospective review of prescribing patterns of four anticonvulsants (valproate, carbamazepine, lamotrigine and topiramate) in women of child bearing age was undertaken. Documented evidence of discussion surrounding teratogenicity and contraceptive issues was sought.</p> <p>Results: Valproate was most commonly prescribed (n=67). Evidence of teratogenic risk counselling at medication initiation was sub-optimal – 40% of individuals prescribed carbamazepine and 22% of valproate. Documentation surrounding contraceptive issues was also low- 17% of individuals prescribed carbamazepine and 13% of valproate.</p> <p>Conclusion: We found both low rates of teratogenic risk counselling and low rates of contraception advice in our cohort. Given the high rates of unplanned pregnancies combined with the relatively high risk of major congenital malformations, it is essential that a detailed appraisal of the risks and benefits associated with anticonvulsant medication occurs and is documented within patients’ psychiatric notes.</p&gt

Detection of ultra-high energy cosmic ray showers with a single-pixel fluorescence telescope

We present a concept for large-area, low-cost detection of ultra-high energy cosmic rays (UHECRs) with a Fluorescence detector Array of Single-pixel Telescopes (FAST), addressing the requirements for the next generation of UHECR experiments. In the FAST design, a large field of view is covered by a few pixels at the focal plane of a mirror or Fresnel lens. We report first results of a FAST prototype installed at the Telescope Array site, consisting of a single 200 mm photomultiplier tube at the focal plane of a 1 m$^2$ Fresnel lens system taken from the prototype of the JEM-EUSO experiment. The FAST prototype took data for 19 nights, demonstrating remarkable operational stability. We detected laser shots at distances of several kilometres as well as 16 highly significant UHECR shower candidates.Comment: Accepted for publication in Astroparticle Physic

A simple and robust method for connecting small-molecule drugs using gene-expression signatures

Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

Formation of Liesegang patterns: A spinodal decomposition scenario

Spinodal decomposition in the presence of a moving particle source is proposed as a mechanism for the formation of Liesegang bands. This mechanism yields a sequence of band positions x_n that obeys the spacing law x_n~Q(1+p)^n. The dependence of the parameters p and Q on the initial concentration of the reagents is determined and we find that the functional form of p is in agreement with the experimentally observed Matalon-Packter law.Comment: RevTex, 4 pages, 4 eps figure

The discontinuous Galerkin method for fractional degenerate convection-diffusion equations

We propose and study discontinuous Galerkin methods for strongly degenerate convection-diffusion equations perturbed by a fractional diffusion (L\'evy) operator. We prove various stability estimates along with convergence results toward properly defined (entropy) solutions of linear and nonlinear equations. Finally, the qualitative behavior of solutions of such equations are illustrated through numerical experiments

Large neutral amino acids in the treatment of PKU: from theory to practice

Notwithstanding the success of the traditional dietary phenylalanine restriction treatment in phenylketonuria (PKU), the use of large neutral amino acid (LNAA) supplementation rather than phenylalanine restriction has been suggested. This treatment modality deserves attention as it might improve cognitive outcome and quality of life in patients with PKU. Following various theories about the pathogenesis of cognitive dysfunction in PKU, LNAA supplementation may have multiple treatment targets: a specific reduction in brain phenylalanine concentrations, a reduction in blood (and consequently brain) phenylalanine concentrations, an increase in brain neurotransmitter concentrations, and an increase in brain essential amino acid concentrations. These treatment targets imply different treatment regimes. This review summarizes the treatment targets and the treatment regimens of LNAA supplementation and discusses the differences in LNAA intake between the classical dietary phenylalanine-restricted diet and several LNAA treatment forms

Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease

Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA). Because acetyl coenzyme A is a key building block for lipid synthesis, we postulated that the inability to catabolize NAA leads to a brain acetate deficiency during a critical period of CNS development, impairing myelination and possibly other aspects of brain development. We tested the hypothesis that acetate supplementation during postnatal myelination would ameliorate the severe phenotype associated with ASPA deficiency using the tremor rat model of Canavan disease. Glyceryltriacetate (GTA) was administered orally to tremor rats starting 7 days after birth, and was continued in food and water after weaning. Motor function, myelin lipids, and brain vacuolation were analyzed in GTA-treated and untreated tremor rats. Significant improvements were observed in motor performance and myelin galactocerebroside content in tremor rats treated with GTA. Further, brain vacuolation was modestly reduced, and these reductions were positively correlated with improved motor performance. We also examined the expression of the acetyl coenzyme A synthesizing enzyme acetyl coenzyme A synthase 1 and found upregulation of expression in tremor rats, with a return to near normal expression levels in GTA-treated tremor rats. These results confirm the critical role played by NAA-derived acetate in brain myelination and development, and demonstrate the potential usefulness of acetate therapy for the treatment of Canavan disease