Massive haemoptysis death and other morbidity associated with high dose rate intraluminal radiotherapy for carcinoma of the bronchus

Fluctuation analysis allows for the determination of mutation rates in cell cultures in vitro. As originally described by Luria and Delbruck and extended by Lea and Coulson and by Capizzi and Jameson, this analysis has been useful in estimating mutation rates in cultured cells where the frequency of mutational events is low. However. in cultures where high mutation rates and multiple independent mutation events occur, leading to the accumulation of many mutant cells, these standard methods may not apply. Here, we present a new method for the estimation of mutation rates based on the assumption that multiple events may contribute to the accumulation of mutant cells. We compared mutation rates determined by Lea and Coulson's and by Capizzi and Jameson's methods with those determined by our method using experimental and stimulated data from our studies of immunoglobulin gene mutation and isotype switching in B lymphocyte cultures. The three methods resulted in very different calculated rates when many mutants were present in the culture, such as when mutation rates were high, while only small differences in calculated rates were found when mutants were rare. Unlike previous fluctuation analysis calculations, our method is applicable for the estimation of both low and high rates.     

The relationship between mineral composition and strength development of high alumina cement

The strength development curves of 1:3 mortars made from high alumina cement (HAC) containing varying proportions of monocalcium aluminate (CA) and pleochroite as determined by Quantitative X-Ray Diffraction (QXRD) have shown that the rapid strength development and high strength is due to CA. Pleochroite will give a high strength, not as high as is obtained from CA, but the strength development is much slower. No recommendation of HAC is implied in this paper dealing with the mineralogy of such cements and relating mineralogy to strength.     

Reflections on replacement

In the United States, the total fertility rate is about 1.9 births per woman, down from a peak of 3.2 a generation ago and below the replacement level of 2.1 children. The proportion of women who will never have children has risen from 8% a generation ago to approximately 18% in 1993. The increase in the proportion of women in the labor force, a proximate explanation of the recent decline in intended fertility, is expected to continue. The demographic consequence is declining population with an older age structure. A pronatalist policy to alleviate this outcome, through monetary transfers from taxpayers to potential parents, is not only unlikely to succeed, it is politically unfeasible. An alternative solution, immediately effective but politically unpalatable, would be a generous immigration policy. Even with replacement level fertility, the population is destined to become much older. This inevitable aging of the population should be countered by appropriate institutional transformations: 1) with lower fertility, a larger proportion of women will be available to participate in the labor force to generate taxes needed to support a larger number of pensioners; 2) the institutional practice of ascribing a dependent status to anyone above a particular age can be changed; 3) concerns that an older labor force will have an obsolete education (and fewer years of it) can be countered by changing access to education. Yet, the most serious question is not merely the net reproduction rate, but producing adequate numbers of new adult citizens with responsibility and technical training in the modern world. The fundamental process of socializing children may be jeopardized by replacing the full-time parent with the hired care-giver, the peer group, and the television set. The attenuation of the bonds between parent and child may devalue the worth of childbearing itself. These portentous consequences deserve consideration.     

Lubrication of Steel/Steel Contacts by Choline Chloride Ionic Liquids

There is a growing interest in the use of ionic liquids to provide lubrication for challenging contacts. This study is an initial assessment of the application of two ionic liquids based on choline chloride cations to be used as ionic liquid lubricants for engineering contacts, in this case steel on steel. These ionic liquids, termed ethaline and reline, have anions of ethylene glycol and urea, respectively, and are available at relatively low costs and in high quantities. In order to assess the lubrication performance of the ionic liquids, lubricated reciprocating sliding wear tests were conducted between M2 tool steel samples and a steel stylus. Initial tests conducted at a sliding speed of 0.005 m s^?1 and 30 N showed that ionic liquids could provide low friction lubrication, comparable to that of SAE 5W30 friction modifier free engine oil under the same test conditions; however, lubrication was lost after short sliding distances. Further testing with higher sliding speed/lower load and varying sample surface textures showed that ionic liquid lubrication could be better maintained in high-speed/low-load testing and by increasing the roughness and therefore surface area of the sample. It was also observed that the choline chloride/urea ionic liquid formed a residual film when tested on iron silicate peened samples, and that this film may promote lubrication.     

Qualitative analysis using Raman spectroscopy and chemometrics: a comprehensive model system for narcotics analysis

The rapid, on-site identification of illicit narcotics, such as cocaine, is hindered by the diverse nature of the samples, which can contain a large variety of materials in a wide concentration range. This sample variance has a very strong influence on the analytical methodologies that can be utilized and in general prevents the widespread use of quantitative analysis of illicit narcotics on a routine basis. Raman spectroscopy, coupled with chemometric methods, can be used for in situ qualitative and quantitative analysis of illicit narcotics; however, careful consideration must be given to dealing with the extensive variety of sample types. To assess the efficacy of combining Raman spectroscopy and chemometrics for the identification of a target analyte under real-world conditions, a large-scale model sample system (633 samples) using a target (acetaminophen) mixed with a wide variety of excipients was created. Materials that exhibit problematic factors such as fluorescence, variable Raman scattering intensities, and extensive peak overlap were included to challenge the efficacy of chemometric data preprocessing and classification methods. In contrast to spectral matching analyte identification approaches, we have taken a chemometric classification model-based approach to account for the wide variances in spectral data. The first derivative of the Raman spectra from the fingerprint region (750-1900 cm(-1)) yielded the best classifications. Using a robust segmented cross-validation method, correct classification rates of better than ～90% could be attained with regression-based classification, compared to ～35% for SIMCA. This study demonstrates that even with very high degrees of sample variance, as evidenced by dramatic changes in Raman spectra, it is possible to obtain reasonably reliable identification using a combination of Raman spectroscopy and chemometrics. The model sample set can now be used to validate more advanced chemometric or machine learning algorithms being developed for the identification of analytes such as illicit narcotics.     

Electrochemical and transport properties of ethaline containing copper and tin chloride

Electrochemical and transport properties were measured for hydrated chloride salts of copper and tin in ethaline, which is a 1∶2 ratio of choline chloride and ethylene glycol. Density, viscosity and conductivity for ethaline melts with different salt concentrations have been measured for temperatures between 293 and 328 K. The change in formal potential with changing metal ion concentration has been determined to evaluate changing speciation in the ionic liquid. Cyclic voltammetry has been carried out to ascertain the reduction potential and diffusion coefficient of the reacting species. For pure ethaline the density was found to decrease by <5% with increase in temperature. On the other hand, the viscosity was found to decrease and conductivity was found to increase by 65% over the same temperature range. The inclusion of metal salts in ethaline had negligible effect on these parameters. Potential measurements showed that copper was reduced through a two-step mechanism and Sn was reduced via a two electron transfer route. The diffusion coefficient values for Cu²⁺ and Sn²⁺ species were 1·22×10^?11 and 1·96×10^?11 m² s^?1 respectively.     

Measurements of Smoke Characteristics in HVAC Ducts

The characteristics of smoke traveling in an HVAC duct have been observed along with the response of selected duct smoke detectors. The simulated HVAC system consists of a 9 m long duct, 0.45 m in diameter. An exhaust fan is placed at one end of the duct and is capable of inducing airflow rates that range from 0 to 1.5 m ³/s. The flow is controlled by means of a manual damper. On the upstream end of the duct there is a square exhaust hood approximately 2.2 m at the bottom and 0.3 m at the top. The bottom of the hood is approximately 2.5 m above the floor a shroud extends down to approximately 1.5 m above the floor. The test section, placed immediately downstream of the hood, is 3.5 m long duct with a square cross section of 0.4 m on a side. The instrumentation includes oxygen, carbon monoxide and carbon dioxide gas analyzers and a load cell to determine the energy release rate of the fires tested. The smoke within the duct is characterized by means of a laser light sheet and charge coupled device (CCD) camera, two white light source and photocell ensembles, a Pitot tube and an array of eight thermocouples placed on the vertical plane of symmetry. A smoke detector was placed at the downstream end of the test section. Two types of detectors were tested, ionization and photoelectric, with a single sampling probe geometry. The fires tested cover a wide range of fuels (propane, heptane, toluene, toluene/heptane mixture, shredded paper, polyurethane foam, wood cribs) with the peak energy release rates up to 800 kW. The smoke detector performance, temperature, flow field, smoke particle size and particle distributions are dependent on the fire characteristics and airflow through the duct. The different measurements could be scaled by means of the fire size and airflow rate but left a strong dependency on the fuel and burning characteristics (i.e., smoldering, flaming). The optical density and mass optical density are analyzed as metrics for characterizing smoke and smoke detector response. Detailed comparisons between the different metrics used are presented throughout this work. Clear evidence of stratification and aging of the smoke along the duct are also presented. The limitations of the present configuration and the need for a larger scale study are also discussed.     

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.