Diaryl dihydropyrazole-3-carboxamides with significant in vivo antiobesity activity related to CB1 receptor antagonism: Synthesis, biological evaluation, and molecular modeling in the homology model

A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compoundsthe bisulfate salt of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (−)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 30showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB1 receptor in the homology model similar to those of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant) 1 and 4S-(−)-3-(4-chlorophenyl)-N-methyl-N‘-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.

Carbon nanotube synthesis from germanium nanoparticles on patterned substrates

Controlled synthesis of carbon nanotubes (CNTs) is highly desirable for nanoelectronic applications. To date, metallic catalyst particles have been deemed unavoidable for the nucleation and growth of any kind of CNTs. Ordered arrays of nanotubes have been obtained by controlled deposition of the metallic catalyst particles. However, the presence of metal species mixed with the CNTs represents a shortcoming for most electronic applications, as metal particles are incompatible with silicon semiconductor technology. In the present paper we report on a metal-catalyst-free synthesis of CNTs, obtained through Ge nanoparticles on a Si(001) surface patterned by nanoindentation. By using acetylene as the carbon feed gas in a low-pressure Chemical Vapor Deposition (CVD) system, multi-walled carbon nanotubes (MWNT) have been observed to arise from the smallest Ge islands. The CNTs and the Ge three-dimensional structures have been analysed by SEM, EDX and AFM in order to assess their elemental features and properties. EDX and SEM results allow confirmation of the absence of any metallic contamination on the surface, indicating that the origin of the CNT growth is due to the Ge nanocrystals.

Towards controlled growth of carbon nanotubes from germanium on nanoindented silicon substrates

In this paper, we report on a metal-catalyst-free synthesis of carbon nanotubes (CNTs) on a pre-patterned Si(001) surface. Arrays of triangular-shaped holes were created by nanoindentation in specific sites of the sample. After germanium deposition and chemical vapor deposition (CVD) of acetylene, a few CNTs nucleated and grew from germanium nanoparticles. These results illustrate that it is possible to control the growth of CNTs without the use of any metal catalyst. By leading the assembly of Ge nanoparticles with a patterning technique, a precise control over the growth order is also attainable.

Modeling intrinsic noise and delays in chemical kinetics of coupled autoregulated oscillating cells

Delays are an important feature in temporal models of genetic regulation due to slow biochemical processes, such as transcription and translation. In this paper, we show how to model intrinsic noise effects in a delayed setting by either using a delay stochastic simulation algorithm (DSSA) or, for larger and more complex systems, a generalized Binomial τ-leap method (Bτ-DSSA). As a particular application, we apply these ideas to modeling somite segmentation in zebra fish across a number of cells in which two linked oscillatory genes (her1 and her7) are synchronized via Notch signaling between the cells.

Electronic functionality in graphene-based nanoarchitectures : discovery and design via first-principles modeling

Graphene has promised many novel applications in nanoscale electronics and sustainable energy due to its novel electronic properties. Computational exploration of electronic functionality and how it varies with architecture and doping presently runs ahead of experimental synthesis yet provides insights into types of structures that may prove profitable for targeted experimental synthesis and characterization. We present here a summary of our understanding on the important aspects of dimension, band gap, defect, and interfacial engineering of graphene based on state-of-the-art ab initio approaches. Some most recent experimental achievements relevant for future theoretical exploration are also covered.

Synthesis of an erodible biomimetic hydrogel for drug delivery using native chemical ligation

Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.

Modeling and analysis of a novel variable-speed cage induction generator

This paper introduces a novel cage induction generator and presents a mathematical model, through which its behavior can be accurately predicted. The proposed generator system employs a three-phase cage induction machine and generates single-phase and constant-frequency electricity at varying rotor speeds without an intermediate inverter stage. The technique uses any one of the three stator phases of the machine as the excitation winding and the remaining two phases, which are connected in series, as the power winding. The two-series-connected-and-one-isolated (TSCAOI) phase winding configuration magnetically decouples the two sets of windings, enabling independent control. Electricity is generated through the power winding at both sub- and super-synchronous speeds with appropriate excitation to the isolated single winding at any frequency of generation. A dynamic mathematical model, which accurately predicts the behavior of the proposed generator, is also presented and implemented in MATLAB/Simulink. Experimental results of a 2-kW prototype generator under various operating conditions are presented, together with theoretical results, to demonstrate the viability of the TSCAOI power generation. The proposed generator is simple and capable of both storage and retrieval of energy through its excitation winding and is expected to be suitable for applications, such as small wind turbines and microhydro systems.

Characteristics of epoxy resin/SiO2 nanocomposite insulation : effects of plasma surface treatment on the nanoparticles

The present study compares the effects of two different material processing techniques on modifying hydrophilic SiO2 nanoparticles. In one method, the nanoparticles undergo plasma treatment by using a custom-developed atmospheric-pressure non-equilibrium plasma reactor. With the other method, they undergo chemical treatment which grafts silane groups onto their surface and turns them into hydrophobic. The treated nanoparticles are then used to synthesize epoxy resin-based nanocomposites for electrical insulation applications. Their characteristics are investigated and compared with the pure epoxy resin and nanocomposite fabricated with unmodified nanofillers counterparts. The dispersion features of the nanoparticles in the epoxy resin matrix are examined through scanning electron microscopy (SEM) images. All samples show evidence that the agglomerations are smaller than 30 nm in their diameters. This indicates good dispersion uniformity. The Weibull plot of breakdown strength and the recorded partial discharge (PD) events of the epoxy resin/plasma-treated hydrophilic SiO2 nanocomposite (ER/PTI) suggest that the plasma-treated specimen yields higher breakdown strength and lower PD magnitude as compared to the untreated ones. In contrast, surprisingly, lower breakdown strength is found for the nanocomposite made by the chemically treated hydrophobic particles, whereas the PD magnitude and PD numbers remain at a similar level as the plasma-treated ones.

Reinforced insulation properties of epoxy resin/SiO2 nanocomposites by atmospheric pressure plasma modification

Nanocomposite dielectrics hold a promising future for the next generation of insulation materials because of their excellent physical, chemical, and dielectric properties. In the presented study, we investigate the use of plasma processing technology to further enhance the dielectric performance of epoxy resin/SiO2 nanocomposite materials. The SiO2 nanoparticles are treated with atmospheric-pressure non-equilibrium plasma prior to being added into the epoxy resin host. Fourier transform infrared spectroscopy (FTIR) results reveal the effects of the plasma process on the surface functional groups of the treated nanoparticles. Scanning electron microscopy (SEM) results show that the plasma treatment appreciably improves the dispersion uniformity of nanoparticles in the host polymer. With respect to insulation performance, the epoxy/plasma-treated SiO2 specimen shows a 29% longer endurance time than the epoxy/untreated SiO2 nanocomposite under electrical aging. The Weibull plots of the dielectric breakdown field intensity suggest that the breakdown strength of the nanocomposite with the plasma pre-treatment on the nanoparticles is improved by 23.3%.

Sub-oxide-to-metallic, uniformly-nanoporous crystalline nanowires by plasma oxidation and electron reduction

Sub-oxide-to-metallic highly-crystalline nanowires with uniformly distributed nanopores in the 3 nm range have been synthesized by a unique combination of the plasma oxidation, re-deposition and electron-beam reduction. Electron beam exposure-controlled oxide → sub-oxide → metal transition is explained using a non-equilibrium model.