Preparation and characterization of chitosan films,crosslinked with symmetric aromatic dianhydrides to achieve enhanced thermal properties

This study has developed a new generation of crosslinked chitosan‐based films using symmetric aromatic dianhydrides as crosslinking agents. The formation of the dianhydride‐crosslinked chitosan hydrogel films was confirmed using Fourier transform infrared and solid‐state ¹³C NMR spectral analyses. The films obtained from these derivatives were characterized by their thermal, swelling and hydrophilic properties. The results showed that introducing a cyclic imide moiety into the chitosan matrices played a significant role in enhancing the thermal properties of these chitosan films. It was found that even at high levels of substitution, thermal stability of the studied chitosan derivatives was improved, in spite of a reduction in crystallinity. Heterocyclic imide linkages produced networks that were insoluble in both acidic and alkaline media but allowed swelling in aqueous media. An increase in the hydrophobicity of the chitosan film surfaces was observed after introduction of the cyclic imide moiety. These engineered films produced noteworthy results concerning their thermal and swelling properties. There is a need to further investigate these films for drug delivery and biomaterials applications. © 2014 Society of Chemical Industry     

Microstructure of mayenite 12CaO·7Al2O3 and electron emission characteristics

Electron emission characteristic, electrical conductivity of polycrystalline mayenite (12CaO·7Al₂O₃) electride, formation of [Ca₂₄Al₂₈O₆₄]⁴⁺(e⁻)₄ framework as a function of phase content, and microstructure have been investigated. The mayenite microstructure was investigated using high-resolution transmission microscopy which revealed the type cage structure of 12CaO·7Al₂O₃ partially filled by extra-framework oxygen ions. Incorporation of electrons by means of carbon ion template 12CaO·7Al₂O₃ produces complex structure, and an incomplete ion template 12CaO·7Al₂O₃ structure consisting of mixture of a [Ca₂₄Al₂₈O₆₄]⁴⁺(e⁻)₄ and [Ca₂₄Al₂₈O₆₄]⁴⁺(O²⁻)₂ framework had a direct effect on the electron emission. Surface chemistry and stability of the 12CaO·7Al₂O₃ electride have been studied using x-ray photoelectron spectroscopy. The work function of phase pure 12CaO·7Al₂O₃ electride was determined from direct thermionic emission data and compared to the measurement from ultraviolet photoelectron spectroscopy (UPS). Depending on the extent of ion template of 12CaO·7Al₂O₃ structure, a work function of 0.9–1.2 eV and 2.1–2.4 eV has been measured and thermionic emission initiating at 600°C.     

Isomeric Carborane Neuromuscular Blocking Agents

We synthesized a family of neuromuscular blocking agents (NMB) based on decamethonium, but containing a carborane cluster in the methylene chain between the two quaternary ammonium groups. The carborane cluster isomers o-NMB, m-NMB, and p-NMB were tested in animals for neuromuscular block and compared with agents used clinically: rocuronium and decamethonium. All three isomers caused reversible muscle weakness in mice as determined by grip strength and inverted screen tests, with a potency rank of p-NMB > rocuronium > decamethonium > m-NMB > o-NMB. The mechanism of action of the compounds was determined by using the in vitro rat phrenic nerve hemi-diaphragm preparation and electrophysiologic measurements in cells. Neostigmine reversed hemi-diaphragm weakness caused by the three isomers and rocuronium, but not succinylcholine. In electrophysiologic recordings of currents through acetylcholine receptor channels, the carborane compounds did not activate channel activity but did inhibit channel activation by acetylcholine. These results demonstrate that the carborane neuromuscular blocking agents are non-depolarizers in contrast to the depolarizing action of the parent compound.     

Mathematical models of the transitions between endocrine therapy responsive and resistant states in breast cancer

Endocrine therapy, targeting the oestrogen receptor pathway, is the most common treatment for oestrogen receptor-positive breast cancers. Unfortunately, these tumours frequently develop resistance to endocrine therapies. Among the strategies to treat resistant tumours are sequential treatment (in which second-line drugs are used to gain additional responses) and intermittent treatment (in which a ‘drug holiday’ is imposed between treatments). To gain a more rigorous understanding of the mechanisms underlying these strategies, we present a mathematical model that captures the transitions among three different, experimentally observed, oestrogen-sensitivity phenotypes in breast cancer (sensitive, hypersensitive and independent). To provide a global view of the transitions between these phenotypes, we compute the potential landscape associated with the model. We show how this oestrogen response landscape can be reshaped by population selection, which is a crucial force in promoting acquired resistance. Techniques from statistical physics are used to create a population-level state-transition model from the cellular-level model. We then illustrate how this population-level model can be used to analyse and optimize sequential and intermittent oestrogen-deprivation protocols for breast cancer. The approach used in this study is general and can also be applied to investigate treatment strategies for other types of cancer.     

Simulation of ductile crack propagation and determination of CTOAs in pipeline steels using cohesive zone modelling

This paper presents recent results of numerical studies on stable crack extension of high toughness steels typical of those in modern gas pipelines using cohesive zone modelling (CZM). The main focus of the work is on the determination of crack‐tip opening angles (CTOAs) of these steels from CZM. Two sets of materials are modelled. The first material set models a typical structural steel, with variable toughness described by four traction–separation (TS) laws. The second set models an X70 pipe steel, with three different TS laws. For each TS law, there are three defining parameters: the maximum cohesive strength, the final separation and the work of separation. The specimens analysed include a crack in an infinite plate (small‐scale yielding, SSY) and a standard drop‐weight tear test (DWTT). Fracture propagation characteristics and values of CTOA are obtained from these two types of specimens. It is shown that cohesive zone models can be successfully used to simulate ductile crack propagation and to numerically measure CTOAs. The ductile crack propagation characteristics and CTOAs obtained from SSY and DWTT specimens are compared for each set of steels. In addition, the CTOA results from numerical CZM of DWTT specimens of X70 steel are compared with those from laboratory tests.     

Using fluorescence-based human androgen receptor gene assay to analyze the clonality of microdissected dendritic cell tumors

The AGT1 permease is a alpha-glucoside-H+ symporter responsible for the active transport of maltose, trehalose, maltotriose, alpha-methylglucoside, melezitose and sucrose. In wild-type as well as in MAL constitutive strains, alpha-methylglucoside seemed to be the best inducer of transport activity, while trehalose had no inducing effect. Based on the initial rates of transport it seems that the sugar preferentially transported by this permease is trehalose, followed by sucrose.     

Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies

Creatine (Cr) and cyclocreatine (cyCr) have been shown to inhibit the growth of a variety of human and murine tumours. The purpose of this study was to evaluate the anti-tumour effect of these molecules in relation to drug accumulation, energy metabolism, tumour water accumulation and toxicity. Nude mice carrying a human colon adenocarcinoma (LS174T) with a creatine kinase (CK) activity of 2.12 units mg(-1) protein were fed Cr (2.5% or 5%) or cyCr (0.025%, 0.1% or 0.5%) for 2 weeks and compared with controls fed standard diet. Cr concentrations of 2.5% and 5% significantly inhibited tumour growth, as did 0.1% and 0.5% cyCr. In vivo 31P magnetic resonance spectroscopy (MRS) after 2 weeks of treatment showed an increase in [phosphocreatine (PCr)+phosphocyclocreatine (PcyCr)]/nucleoside triphosphate (NTP) with increasing concentrations of dietary Cr and cyCr, without changes in absolute NTP contents. The antiproliferative effect of the substrates of CK was not related to energy deficiency but was associated with acidosis. Intratumoral substrate concentrations (measured by 1H-MRS) of 4.8 micromol g(-1) wet weight Cr (mice fed 2.5% Cr) and 6.2 micromol g(-1) cyCr (mice fed 0.1% cyCr) induced a similar decrease in growth rate, indicating that both substrates were equally potent in tumour growth inhibition. The best correlant of growth inhibition was the total Cr or (cyCr+Cr) concentrations in the tissue. In vivo, these agents did not induce excessive water accumulation and had no systemic effects on the mice (weight loss, hypoglycaemia) that may have caused growth inhibition.     

A random generator of resource-constrained multi-project network problems

Many scheduling problems in project management, manufacturing, and elsewhere require the generation of activity networks to test proposed solution methods. Single-network generators have been used for the resource-constrained project scheduling problem (RCPSP). Since the first single-network generator was proposed in 1993, several advances have been reported in the literature. However, these generators create only one network or project at a time; they cannot generate multi-project problems to desired specifications. This paper presents the first multi-network problem generator. It is especially useful for investigating the resource-constrained multi-project scheduling problem (RCMPSP), where a controlled set of multi-project test problems is crucial for analyzing the performance of solution methods. In addition to the single-project characteristics handled by existing network generators—such as activity duration, resource types and usage, and network size, shape, and complexity—the proposed generator produces multi-project portfolios with controlled resource distributions and amounts of resource contention. To enable the generation of projects with desired levels of network complexity, we also develop several theoretical insights on the effects of network topology on the probability of successful network generation. Finally, we generate 12,320 test problems for a full-factorial experiment and use analysis of means to conclude that the generator produces “near-strongly random” problems. Fully “strongly random” problems require much greater computational expense.