Biological Evaluation of Products Formed from the Irradiation of Chlorpromazine with a 266 nm Laser Beam

Models that can predict consumer choices are essential technical support fordecision makers in many contexts. The focus of this thesis is to address predictionproblems in discrete choice models and to develop methods to increase the predictivepower of these models with application to car type choice. In this thesis we challengethe common practice of prediction that is using statistical inference to estimateand select the ‘best’ model and project the results to a future situation. We showthat while the inference approaches are powerful explanatory tools in validating theexisting theories, their restrictive theory-driven assumptions make them not tailormadefor predictions. We further explore how modeling considerations for inferenceand prediction are different.Different papers of this thesis present various aspects of the prediction problemand suggest approaches and solutions to each of them.In paper 1, the problem of aggregation over alternatives, and its effects on bothestimation and prediction, is discussed. The focus of paper 2 is the model selectionfor the purpose of improving the predictive power of discrete choice models. Inpaper 3, the problem of consistency when using disaggregate logit models for anaggregate prediction question is discussed, and a model combination is proposedas tool. In paper 4, an updated version of the Swedish car fleet model is appliedto assess a Bonus-Malus policy package. Finally, in the last paper, we present thereal world applications of the Swedish car fleet model where the sensitivity of logitmodels to the specification of choice set affects prediction accuracy.QC 20160115</p

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

INTRODUCTION: Phenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser. METHODS: Varying concentrations of Chlorpromazine Hydrochloride (CPZ) (2-20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1-24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200-1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC)-Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923. RESULTS: CPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified. CONCLUSIONS: Exposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is "clean" and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives

Absorption spectra of the irradiated products per unit period of time.

<p>Irradiation of 2 mg/mL of CPZ for intervals of A) 30 minutes up to 240 minutes at E = 1 mJ and B) Irradiation of 2 mg/mL of CPZ from 1 to 240 minutes at E = 6.5 mJ. Note: After irradiation, an aliquot of the contents of the cuvette was diluted to 0.2 mg/mL and the shown absorption spectra were measured. Due to the fact that the absorption peaks are quite broad and the experimental errors to assign their wavelength are associated with the peaks spectral widths, the peak absorbance of control, un-irradiated CPZ varied from 254 to 256 nm.</p

HPLC-DAD chromatograms of un-irradiated 2 mg/mL of CPZ (A) and 2 mg/mL of CPZ irradiated for time periods of 1 (B), 5 (C), 15 (D), 30 (E), 60 (F), 120 (G) and 240 (H) minutes, recorded at the maximum absorbance in the wavelength range of λ = 230–450 nm.

<p>Note: intensity scales are not identical; overall amount of UV-active material is gradually decreasing with the irradiation time.</p