X-ray crystal structure and molecular mechanics calculations of (2,6-iso-dipropyl-phenylamide) dimethyl (tetra-methylcyclopenta-dienyl) silane titanium dichloride

Crystal and molecular structure of (2.6-dipropylphenylamide) dimethyl (tetra-methyl cyclopentadienyl) silane titanium dichloride (I) was fully characterized by X-ray diffraction. The crystal is obtained from a mixture of ether/hexane as orthorhombic. with a = 12.658 (3) Angstrom. b = 16.62 (3) Angstrom. c = 11.760 (2) Angstrom. V = 2474.2 (9) Angstrom(3). Z = 4, space group Pnma. R = 0.0399; Componud I compose of the pi-bounded ring with its dimethylsilyl-dipropyl phenyl amido group and the two terminal chloride atoms coordinated to central metal to form a so-called constrained geometry catalyst (CGC) structure. The result of molecular mechanics (MM) calculations on compound I shows that bond lengths and bond angles from the MM calculation are comparable to the data obtained from the X-ray diffraction study. The relation of the structure of CGCs and their catalytic activity by MM calculations is also discussed.

Artificial neural network applied to diagnosis of lung cancer

Artificial neural network(ANN) approach was applied to classification of normal persons and lung cancer patients based on the metal content of hair and serum samples obtained by inductively coupled plasma atomic emission spectrometry (ICP-AES) for the two groups. This method was verified with independent prediction samples and can be used as an aiding means of the diagnosis of lung cancer. The case of predictive classification with one element missing in the prediction samples was studied in details, The significance of elements in hair and serum samples for classification prediction was also investigated.

EFFECT OF REPTATION ON FRACTURE-MECHANICS OF RUBBER NETWORKS

End-linked hydroxyl-terminated polybutadiene containing unattached linear polybutadiene was used to study the effect of reptating species on the fracture mechanics of rubber networks. The concentration of reptating species in the networks ranged from 0 to 100%. The fracture mechanics of the networks was described using the critical strain energy release rate in mode III testing, i.e. the tearing energy. The tearing energy was measured at room temperature using a 'trouser' specimen at a strain rate spanning five logarithmic decades. When the strain rate was as low as 10(-4) s-1, the tearing energy of the networks increased with reduction in reptating species. In this case the reptating species did not contribute to the tearing energy of the networks due to relaxation. Hence, the tearing energy increased with the number of crosslinked chains per unit volume in the networks. At a strain rate ranging from 10(-3) to 10(-1) s-1, the tearing energy of the networks was governed by local viscosity. The tearing energies of the networks containing various amounts of reptating species were superimposed to give a master curve based on the Williams-Landel-Ferry equation.

A study of a molecular mechanics field used in simulating enantiorecognition

A molecular mechanics field, Alchemy II, was utilized to model the chiral recognition between S-N-acetyl-alpha-methyl-alpha-naphthylamine and (R, S)-N-(3, 5-dinitrophrnyl)-alpha-methyl-benzeneacetamide and between beta-cyclodextrin and (R, S)-fenoprofen. Some preliminary results have: been obtained to sustain the three-point action models and the induce-fit action in enantiorecognition.

Qualitative and Quantitative Knowledge in Classical Mechanics

This thesis investigates what knowledge is necessary to solve mechanics problems. A program NEWTON is described which understands and solves problems in mechanics mini-world of objects moving on surfaces. Facts and equations such as those given in mechanics text need to be represented. However, this is far from sufficient to solve problems. Human problem solvers rely on "common sense" and "qualitative" knowledge which the physics text tacitly assumes to be present. A mechanics problem solver must embody such knowledge. Quantitative knowledge given by equations and more qualitative common sense knowledge are the major research points exposited in this thesis. The major issue in solving problems is planning. Planning involves tentatively outlining a possible path to the solution without actually solving the problem. Such a plan needs to be constructed and debugged in the process of solving the problem. Envisionment, or qualitative simulation of the event, plays a central role in this planning process.

Expression of C-reactive protein in human lung epithelial cells and up-regulation by cytokines and carbon particles.

C-reactive protein (CRP) is the prototypic human acute-phase protein and is found at increased levels in the blood during episodes of inflammation. CRP was generally thought to be produced only by hepatocytes; however, several studies have shown extrahepatic synthesis of CRP. A previous study showed that PM10 and ultrafine carbon black (ufCB) were able to induce CRP expression in A549 cells. This study aims to examine the factors that lead to the production of CRP in A549 cells. A549 human lung epithelial cells were treated with cytokines (interleukin 6, tumor necrosis factor , interferon , or interleukin 1) or carbon particles (CB and ufCB) for 18 h. It was found that CRP could be expressed within the cells and that CRP was secreted from the cells particularly with tumor necrosis factor , CB and ufCB treatments. It was also found that this expression of CRP with CB and ufCB treatments was dependent on nuclear factor kappa B (NFB). The expression of CRP in A549 cells may indicate an important role for CRP expression and secretion from lung epithelial cells in response to inflammatory stimuli.

Automatic 3D Registration of Lung Surfaces in Computed Tomography Scans

We developed an automated system that registers chest CT scans temporally. Our registration method matches corresponding anatomical landmarks to obtain initial registration parameters. The initial point-to-point registration is then generalized to an iterative surface-to-surface registration method. Our "goodness-of-fit" measure is evaluated at each step in the iterative scheme until the registration performance is sufficient. We applied our method to register the 3D lung surfaces of 11 pairs of chest CT scans and report promising registration performance.

Computing a Uniform Scaling Parameter for 3D Registration of Lung Surfaces

A difficulty in lung image registration is accounting for changes in the size of the lungs due to inspiration. We propose two methods for computing a uniform scale parameter for use in lung image registration that account for size change. A scaled rigid-body transformation allows analysis of corresponding lung CT scans taken at different times and can serve as a good low-order transformation to initialize non-rigid registration approaches. Two different features are used to compute the scale parameter. The first method uses lung surfaces. The second uses lung volumes. Both approaches are computationally inexpensive and improve the alignment of lung images over rigid registration. The two methods produce different scale parameters and may highlight different functional information about the lungs.

Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth offers a considerable degree of protection from a wide variety of challenges such as the host immune system or antibiotic therapy. The threat posed by the emergence of chronic pathogens is prompting the development of next generation antimicrobials. The biofilm mode of growth is often central to the establishment of chronic infection and the development of antibiotic resistance. Thus, targeting biofilm formation has emerged as one of the principle strategies for the development of next generation antimicrobials. In this thesis two separate approaches were used to identify potential anti - biofilm targets. The first strategy focused on the identification of novel genes with a role in a biofilm formation. High throughput screening identified almost 300 genes which had a role in biofilm formation. A number of these genes were characterised at a phenotypic and a molecular level. The second strategy focused on the identification of compounds capable of inhibiting biofilm formation. A collection of marine sponge isolated bacteria were screened for the ability to inhibit the central pathway regulating biofilm formation, quorum sensing. A number of distinct isolates were identified that had quorum sensing inhibition activity from which, a Pseudomonas isolate was selected for further characterisation. A specific compound capable of inhibiting quorum sensing was identified using chemical analytical technologies in the supernatant of this marine isolate.

The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung

There is an increasing appreciation of the polymicrobial nature of bacterial infections associated with Cystic Fibrosis (CF) and of the important role for interactions in influencing bacterial virulence and response to therapy. Patients with CF are co-infected with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are cis-2-unsaturated fatty acids. Previous studies showed that DSF from S. maltophilia leads to altered biofilm formation and increased tolerance to antibiotics in P. aeruginosa and that these responses require the P. aeruginosa sensor kinase PA1396. The work in this thesis aims of further elucidate the influence and mechanism of DSF signalling on P. aeruginosa and examine the role that such interspecies signalling play in infection of the CF airway. Next generation sequencing technologies targeting the 16S ribosomal RNA gene were applied to DNA and RNA isolated from sputum taken from cohorts of CF and non-CF subjects to characterise the bacterial community. In parallel, metabolomics analysis of sputum provided insight into the environment of the CF airway. This analysis revealed a number of observations including; that differences in metabolites occur in sputum taken from clinically stable CF patients and those with exacerbation and DNA- and RNA-based methods suggested that a strong relationship existed between the abundance of specific strict anaerobes and fluctuations in the level of metabolites during exacerbation. DSF family signals were also detected in the sputum and a correlation with the presence of DSFproducing organisms was observed. To examine the signal transduction mechanisms used by P. aeruginosa, bioinformatics with site directed mutagenesis were employed to identify signalling partners for PA1396. A pathway suggesting a role for a number of proteins in the regulation of several factors following DSF recognition by PA1396 were observed.

Paradoxical worsening of tuberculosis in a heart-lung transplant recipient.

We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments. METHODS: Using sequential bronchoalveolar lavages, we assessed the inflammatory response in the lung and investigated the alveolar immune response against a Mycobacterium tuberculosis antigen. RESULTS: The paradoxical reaction was characterized by a massive infiltration of the alveolar space by M. tuberculosis antigen-specific CD4(+) T cells and by the presence of a CD4(-)CD8(-) T lymphocyte subpopulation bearing phenotypic markers (CD16(+)/56(+)) classically associated with NK cells. CONCLUSION: This case report illustrates that even solid organ transplant recipients receiving intense triple-drug immune suppression may be able to develop a paradoxical reaction during TB treatment. Transplant physicians should be aware of this phenomenon in order to differentiate it from treatment failure.

Characterization of the morphonuclear features and DNA ploidy of typical and atypical carcinoids and small cell carcinomas of the lung

The authors analyzed several cytomorphonuclear parameters related to chromatin distribution and DNA ploidy in typical and atypical carcinoids and in small cell lung cancers. Nuclear measurements and analysis were performed with a SAMBA 200 (TITN, Grenoble, France) cell image processor with software allowing the discrimination of parameters computed on cytospin preparations of Feulgen-stained nuclei extracted from deparaffinized tumor tissues. The authors' results indicate a significant increase in DNA content--assessed by integrated optical density (IOD)--from typical carcinoids to small cell lung carcinomas, with atypical carcinoids showing an intermediate value. Parameters related to hyperchromatism (short and long run length and variance of optical density) also characterize the atypical carcinoids as being intermediate between typical carcinoids and small cell lung cancers. The systematic measurement of these cytomorphonuclear parameters seems to define an objective, reproducible "scale" of differentiation that helps to define the atypical carcinoid and may be of value in establishing cytologic criteria for differential diagnosis.