Artificial neural networks

A general neural network model is introduced. The authors begin with a discussion of models for both individual neurons and for networks of neurons. A common learning rule, i.e. backward error propagation, also known as backpropagation, is described briefly and applied to an example problem     

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation,characterization, in vitro,and in vivo study

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD₅₀). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.     

Nanoparticle effects on spherulitic structure and phase formation in polypropylene crystallized at moderately elevated pressures: The influence on fracture resistance

We report here for the first time the changes in spherulitic structure and phase formation that occur in polypropylene in the presence of nanoclay on crystallization at high pressures. To delineate the effects of pressure and nanoclay on the crystallization behavior, polypropylene with and without nanoclay were studied under identical experimental conditions. The two important findings are (i) the spherulite size and morphology of polypropylene in the absence and presence of nanoclay is a function of the crystallization pressure and (ii) at constant crystallization pressure, the presence of nanoclay reduced the spherulite size from 155 μm to 19 μm at 0.1 MPa. Another important observation was the evidence of γ-phase in polypropylene with nanoclay at pressures between 0.1 MPa and 59 MPa. In neat polypropylene, increasing crystallization pressure changed the deformation process from vein-type crazing to fibrillation, while in polypropylene-containing 4 wt.% clay, an increased tendency towards fibrillated fracture with increase in crystallization pressure was observed. At the present time, the observations imply the following possibilities for future considerations: (a) nanoclay changes the equilibrium state of the polymer chain or its conformation and (b) nanoclay provides a surface that is favorable for possible epitaxial growth of γ-phase because the lattice mismatch is <10%. The observed nanoparticle and pressure-induced effects, namely dramatic reduction in spherulite size and γ-phase appears to be beneficial for impact strength with consequent change in the micromechanism of plastic deformation.     

Thermal stability study of Pd-composite membrane fabricated by surfactant induced electroless plating (SIEP)

Over the years, several different methods have been developed by modifying the conventional electroless plating (CEP) technique to fabricate dense thin Pd composite membranes with high H₂ permselectivity. In this study, Pd composite membranes on macroporous stainless steel substrate (MPSS) were fabricated using CEP and novel surfactant induced electroless plating (SIEP) methods. The structural characteristics of CEP and SIEP fabricated Pd membranes were investigated before and after the heat treatment using SEM, XRD, EDS, and AFM techniques. The H₂ permselectivity performance of the SIEP membranes was compared with that of CEP at different temperatures and trans-membrane pressures in the range of 523-823 K and 20-100 psi, respectively. The long-term thermal stability test of SIEP fabricated membranes was carried out on two different membranes, fabricated on MPSS substrates with and without oxide layer at 15 psi trans-membrane pressure and thermal cycling of 573-723-573 K. The microstructure analysis revealed that SIEP membranes have finer grains and diffused grain boundaries resulting in uniform, smooth, continuous, and pinhole free Pd-film. The SIEP membrane showed eight-fold higher H₂ flux (1.7172 mol/m²/s) and four-fold higher H₂ selectivity (~148) at 823 K and 100 psi trans-membrane pressure, compared to CEP membrane. Pd/MPSS membrane subjected to test for long-term performance and thermal cycling showed stable performance up to 1200 h while maintaining infinite H₂ selectivity. Interestingly, although the thickness of Pd/oxi-MPSS (13.49 µm) membrane was higher than that of Pd/MPSS (11.6 µm) membrane, the H₂ flux of Pd/oxi-MPSS membrane was two times higher than that of Pd/MPSS, attributed to the effective action of oxide layer as diffusion barrier.     

Cytoplasmic domains mediate the ligand-induced affinity shift of guanylyl cyclase C

Guanylyl cyclase C (GCC), the receptor for the Escherichia coli heat-stable enterotoxin (ST), exhibits multiple binding affinities, including high (RH) and low (RL) affinity sites and a ligand-induced conversion of low-affinity sites from a higher (RL1) to a lower (RL2) affinity state. Occupancy of the lowest affinity state of low-affinity sites is coupled to ligand-induced catalytic activation. In the present studies, ligand binding and catalytic activation properties of a series of intracellular deletion mutants of GCC were examined to identify the structural domains underlying expression of high- and low-affinity sites and the ligand-induced shift in low-affinity sites. These studies demonstrated that the cytoplasmic domains of GCC are not required, but extracellular and transmembrane domains are sufficient, for expression of high-affinity binding sites. In addition, the cytoplasmic juxtamembrane and kinase homology domains are required for expression of the ligand-induced affinity shift in low-affinity sites. Of significance, this shift in affinity was insensitive to adenine nucleotides, in contrast to other members of the receptor guanylyl cyclase family, such as guanylyl cyclase A (GCA). Also, the juxtamembrane and kinase homology domains are critical for coupling ST-receptor binding and guanylyl cyclase catalytic activation. Indeed, deletion of those domains from GCC results in a constitutively inhibited enzyme, suggesting that they function as positive effectors of ligand activation, in contrast to GCA and GCB, in which the kinase homology domain represses basal catalytic activity. These data suggest that the mechanisms regulating different members of the receptor guanylyl cyclase family are overlapping but not identical.     

Rat guanylyl cyclase C expressed in COS-7 cells exhibits multiple affinities for Escherichia coli heat-stable enterotoxin

Intestinal cells exhibit binding sites with different affinities for Escherichia coli heat-stable enterotoxin (ST) and guanylin, suggesting the existence of different receptors for these peptides. Guanylyl cyclase C from intestinal cells has been identified as one receptor for these peptides. Equilibrium and kinetic binding characteristics of rat guanylyl cyclase C expressed in COS-7 cells were examined, employing ST, to determine if this receptor exhibited multiple affinities. Scatchard analysis of equilibrium binding yielded curvilinear isotherms consistent with the presence of high (pM) and low (nM) affinity sites. Kinetic analysis of binding demonstrated that these sites exhibited similar dissociation but different association kinetics. In addition, two distinct affinity states of low affinity sites were identified with dissociation constants of 0.15 and 5.85 nM. Association of ST and low affinity sites was biphasic, while dissociation from these sites was unimodal. Close agreement of equilibrium and kinetic dissociation constants suggested that low affinity sites were in the lowest affinity state at equilibrium. Comparison of the ligand dependence of guanylyl cyclase activity (EC50 = 110 nM) with receptor occupancy revealed that binding of ST to the lowest affinity state of low affinity sites (EC50 = 80 nM) is directly coupled to catalytic activation. These studies suggest that binding sites with different affinities for ST exhibited by intestinal cells reflect the expression of a single gene product, guanylyl cyclase C, rather than different receptors for the ligand. The shift in affinity state of low affinity sites and its correlation with catalytic activation suggest a central role for this phenomenon in mechanisms mediating receptor-effector coupling of membrane guanylyl cyclases.     

GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

Objective

Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein.

Materials and methods

Motion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a d-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T.

Results

In high-grade gliomas with BBB leakage, d-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor.

Conclusion

First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

     

Microbial reduction of sulfur dioxide and nitric oxide

Two process concepts have been developed for a microbial contribution to the problem of flue gas desulfurization and NO_x removal. We have demonstrated that the sulfate-reducing bacterium Desulfovibrio desulfuricans can be grown in a mixed culture with fermentative heterotrophs in a medium in which glucose served as the only carbon source. Beneficial cross-feeding resulted in vigorous growth of D. desulfuricans, which used SO₂(g) as a terminal electron acceptor, with complete reduction of SO₂ to H₂S in 1–2 s of contact time. We have proposed that the concentrated SO₂ stream, obtained from regeneration of the sorbent in regenerable processes for flue gas desulfurization, could be split with two-thirds of the SO₂ reduced to H₂S by contact with a culture of sulfate-reducing bacteria. The resulting H₂S could then be combined with the remaining SO₂ and used as feed to a Claus reactor to produce elemental sulfur. However, the use of glucose as an electron donor in microbial SO₂ reducing cultures would be prohibitively expensive. Therefore, if microbial reduction of SO₂ is to be economically viable, less expensive electron donors must be found. Consequently, we have evaluated the use of municipal sewage sludge and elemental hydrogen as carbon and/or energy sources for SO₂ reducing cultures. Heat and alkali pretreated sewage sludge has been successfully used as a carbon and energy source to support SO₂ reduction in a continuous, anaerobic mixed culture containing D. desulfuricans. The culture operated for nine months with complete reduction of SO₂ and H₂S. Another sulfate-reducing bacterium, Desulfotomaculum orientis, has also been grown in batch cultures on a feed of SO₂, H₂ and CO₂. Complete reduction of SO₂ to H₂S was observed with gas-liquid contact times of 1–2 s. We have also demonstrated that the facultative anaerobe and chemoautotroph, Thiobacillus denitrificans, can be cultured anoxically in batch reactors using NO(g) as a terminal electron acceptor with reduction to elemental nitrogen. We have proposed that the concentrated stream of NO_x, as obtained from certain regenerable processes for flue gas desulfurization and NO_x removal, could be converted to elemental nitrogen for disposal by contact with a culture T. denitrificans. Two heterotrophic bacteria have also been identified which may be grown in batch cultures with succinate or heat and alkali pretreated sewage sludge as carbon and energy sources and NO as a terminal electron acceptor. These are Paracoccus denitrificans and Pseudomonas denitrificans.     

Synthesis and Characterization of ZnO/CuO Nanocomposites as an Effective Photocatalyst and Gas Sensor for Environmental Remediation

Journal of Inorganic and Organometallic Polymers and Materials - Current study delineates the synthesis and environmental applications of ZnO/CuO nanocomposite in photocatalysis and gas sensing....