Artificial neural networks with quasipolynomial synapses and product synaptic contacts

A neural network model with quasipolynomial synapses and product contacts is investigated. The model further generalizes the sigma-pi and product unit models. What and how many quasipolynomial terms, both for individual variables and for cross-product terms, are learned, not predetermined, subject to hardware constraint. Three possible cases are considered. In case 1, the number of learnable parameters needed is determined in learning. It can be considered another method of growing a network for a given task, although the graph of the network is fixed. Mechanisms preventing the network from growing too many parameters are designed. In cases 2 and 3, the number of parameters allowed or available is fixed. Cases 2 and 3 may offer both some control on the generalizability of learning and flexibility in functional representation, and may provide a compromise between the complexity of loading and generalizability of learning. Gradient-descent algorithms for training feedforward networks with polynomial synapses and product contacts are developed. Hardware issues are considered, and experimental results are presented.On leave from the School of Computer Science, Technical University of Nova Scotia, Canada     

Stereospecific determination of mefloquine in biological fluids by high-performance liquid chromatography

A sensitive stereoselective HPLC method was developed for determination of mefloquine (MFQ) enantiomers in plasma, urine and whole blood. The assay involved liquid-liquid extraction of MFQ from biological fluids with a mixture of hexane and isopropanol in the presence of sodium hydroxide and derivatization of the residue by (+)-(S)-naphthylethylisocyanate (NEIC) as chiral derivatizing reagent. Separation of the resulting diastereomers was performed on a silica normal-phase column using chloroform-hexane-methanol (25:74:1) as the mobile phase with a flow-rate of 1 ml/min. Using 200 μl of plasma or whole blood, the limit of determination was 0.2 μg/ml with UV detection for both enantiomers. The limit of determination in 500 μl of urine was 0.08 μg/ml with UV detection.     

Evidence of absorption rate dependency of ibuprofen inversion in the rat

Ibuprofen (IB) is a chiral 2-arylpropionic acid derivative used as a nonsteroidal antiinflammatory drug (NSAID). It undergoes substantial R to S chiral inversion in humans and rats. In addition to systemic inversion, presystemic chiral inversion has been suggested for IB in humans but only after administration of formulations with slow absorption rates. In search for a suitable animal model, the absorption rate dependency of the extent of inversion was examined in male Sprague–Dawley rats given 20 mg/kg of racemic IB in aqueous solution (T_max, 0.6 h), suspension (T_max, 1 h) or as sustained release granules (T_max, 2.3 h). In addition, (R)-IB (5 mg/liter) was incubated in the presence of everted rat gut segments in an organ bath at 37°. After sustained release granules, the S:R AUC ratios (7.3 ± 1.5) were significantly higher than suspension (3.6 ± 1.1) and solution (3.5 ± 0.2). Accordingly, AUC_S and AUC_R, as percent of the total AUC (S + R), significantly increased and decreased, respectively, after administration of the sustained released granules as compared with the solution and suspension. A significant positive linear correlation was found between the S:R AUC ratios and the corresponding T_max for (R)-IB (r = 0.82). In vitro, (R)-IB was inverted by everted jejunum (12.2 ± 1.6%), ileum (14.2 ± 2.0%), and colon (4.4 ± 0.6%) segments. IB was also glucuronidated in the presence of the intestinal segments. Therefore, similar to earlier observations made in humans, in the rat, the S:R AUC ratio was positively and significantly correlated with the absorption rate from the dosage form. Rat small intestine was capable of inverting and conjugating (R)-IB. Hence, rat is a suitable model for studying the chiral inversion of IB. © 1994 Wiley-Liss, Inc.     

Severely damaged kidneys possess multipotent renoprotective stem cells

Background aimsTissue-specific stem cells are a promising target for kidney regeneration, because it has been shown that they play a primary role in kidney repair. Several methods have been developed for the isolation of stem/progenitor cells from healthy kidneys but the existence of these cells in chronically damaged kidneys has not been noticed so far.MethodsA mouse model of chronic kidney failure was developed by ligation of the left ureter for 5 months, and then isolation of stem cells from this tissue as well as normal kidneys was attempted.ResultsWe found that multipotent stem cells could be isolated from both types of tissue. In addition, the cells isolated from damaged kidneys showed potential for homing to the site of injury and a renoprotective effect in an animal model of cisplatin-induced nephropathy.ConclusionsThese results show that multipotent renoprotective stem cells exist in severely damaged kidneys, which could be a target for designing new therapies.     

Reduced efficacy of multiple doses of CpG-matured dendritic cell tumor vaccine in an experimental model

CpG motifs have been advanced as agents that stimulate the maturation of DCs for immunotherapy. The present study tested the hypothesis that multiple doses of CpG-matured DC vaccine would be efficacious for complete eradication of experimentally-induced tumor. Accordingly, WEHI164 cells were implanted subcutaneously in the flank of BALB/c mice. During DC culture, tumor lysate was added to immature DCs followed by addition of CpG or non-CpG control 4–6 h later. A total of three doses of CpG or non-CpG control-matured DCs were injected around tumors. The results showed that multiple doses of CpG-matured DCs led to considerable decrease in cytotoxicity of lymphocytes and significantly increased tumor growth rate compared to a single dose. Further, mice which received three doses of the vaccine also displayed significant FoxP3 in tumor tissue. In conclusion, multiple doses of CpG-matured DCs exhibited decreased anti-tumor immunity in association with increased expression of FoxP3.     

Evaluation of Cadmium, Chromium, Nickel, and Zinc in Biological Samples of Psoriasis Patients Living in Pakistani Cement Factory Area

Psoriasis is a noncontiguous common and chronic skin disorder. The aim of the present study was to compare the level of trace elements cadmium (Cd), chromium (Cr), Nickel (Ni), and zinc (Zn) in biological samples (whole blood, urine, and scalp hair) of psoriasis patients of both gender age ranged (25–55 years) at mild, moderate severe, and more severe stage (n?=?418) living in the vicinity of cement factory. For comparison purposes, healthy age-matched referent subjects, residents of industrial and non-industrial area, of both gender were also selected (n?=?241). The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The validity and accuracy of methodology was checked by using certified reference materials (CRMs) and conventional wet acid digestion method on same CRMs and real samples. The results of this study showed that the mean values of Cd, Cr, Ni, and Pb were significantly higher in scalp hair, blood, and urine samples of mild and severe psoriasis patients as compared to referents (p?<?0.001), while the concentration of Zn was lower in the scalp hair and blood, but higher in the urine samples of psoriasis patients. The deficiency of Zn in psoriasis patients may be undoubtedly caused by the toxic element exposures via cement factory.     

Evaluation of Status of Cadmium, Lead, and Nickel Levels in Biological Samples of Normal and Night Blindness Children of Age Groups 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood trace metals toxicity, which is the most common problem found in underdeveloped countries. This study was designed to compare the levels of cadmium (Cd), lead (Pb), and nickel (Ni) in scalp hair, blood, and urine of night blindness children age ranged 3–7 and 8–12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of Cd, Pb, and Ni in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cd, Pb, and Ni by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cd, Pb, and Ni in the biological samples (blood, scalp hair, and urine) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating toxicity of trace metals in biological samples of night blindness children.     

Evaluation of Status of Zinc, Copper, and Iron Levels in Biological Samples of Normal Children and Children with Night Blindness with Age Groups of 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. This study was designed to compare the levels of zinc (Zn), copper (Cu), and iron (Fe) in scalp hair, blood, and urine of both genders of children with night blindness with age range of 3–7 and 8–12 years, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of zinc, copper, and iron in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cu, Fe, and Zn by flame atomic absorption spectrometry using an air/acetylene flame. The results indicated significantly lower levels of Fe, Cu, and Zn in the biological samples (blood and scalp hair) of male and female children with night blindness, compared with control subjects of both genders. These data present guidance to clinicians and other professionals investigating the deficiency of essential trace metals in biological samples (scalp hair and blood) of children with night blindness.     

Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots

Mental retardation (MR) has a worldwide prevalence of around 2% and is a frequent cause of severe disability. Significant excess of MR in the progeny of consanguineous matings as well as functional considerations suggest that autosomal recessive forms of MR (ARMR) must be relatively common. To shed more light on the causes of autosomal recessive MR (ARMR), we have set out in 2003 to perform systematic clinical studies and autozygosity mapping in large consanguineous Iranian families with non-syndromic ARMR (NS-ARMR). As previously reported (Najmabadi et al. in Hum Genet 121:43-48, 2007), this led us to the identification of 12 novel ARMR loci, 8 of which had a significant LOD score (OMIM: MRT5-12). In the meantime, we and others have found causative gene defects in two of these intervals. Moreover, as reported here, tripling the size of our cohort has enabled us to identify 27 additional unrelated families with NS-ARMR and single-linkage intervals; 14 of these define novel loci for non-syndromic ARMR. Altogether, 13 out of 39 single linkage intervals observed in our cohort were found to cluster at 6 different loci on chromosomes, i.e., 1p34, 4q27, 5p15, 9q34, 11p11-q13 and 19q13, respectively. Five of these clusters consist of two significantly overlapping linkage intervals, and on chr 1p34, three single linkage intervals coincide, including the previously described MRT12 locus. The probability for this distribution to be due to chance is only 1.14 × 10(-5), as shown by Monte Carlo simulation. Thus, in contrast to our previous conclusions, these novel data indicate that common molecular causes of NS-ARMR do exist, and in the Iranian population, the most frequent ones may well account for several percent of the patients. These findings will be instrumental in the identification of the underlying genes.     

The Importance of Termites to the CH<Subscript>4</Subscript> Balance of a Tropical Savanna Woodland of Northern Australia

Termites produce methane (CH₄) as a by-product of microbial metabolism of food in their hindguts, and are one of the most uncertain components of the regional and global CH₄ exchange estimates. This study was conducted at Howard Springs near Darwin, and presents the first estimate of CH₄ emissions from termites based on replicated in situ seasonal flux measurements in Australian savannas. Using measured fluxes of CH₄ between termite mounds and the atmosphere, and between soil and the atmosphere across seasons we determined net CH₄ flux within a tropical savanna woodland of northern Australia. By accounting for both mound-building and subterranean termite colony types, and estimating the contribution from tree-dwelling colonies it was calculated that termites were a CH₄ source of +0.24 kg CH₄-C ha⁻¹ y⁻¹ and soils were a CH₄ sink of −1.14 kg CH₄-C ha⁻¹ y⁻¹. Termites offset 21% of CH₄ consumed by soil resulting in net sink strength of −0.90 kg CH₄-C ha⁻¹ y⁻¹ for these savannas. For Microcerotermes nervosus (Hill), the most abundant mound-building termite species at this site, mound basal area explained 48% of the variation in mound CH₄ flux. CH₄ emissions from termites offset 0.1% of the net biome productivity (NBP) and CH₄ consumption by soil adds 0.5% to the NBP of these tropical savannas at Howard Springs.