Infrared and Raman spectroscopic studies of matrix isolated amines

This thesis describes the infrared and Raman spectroscopic studies on ammonia, methylamine and ethylamine in low temperature argon and nitrogen matrices.The initial aim was to classify qualitatively and quantitatively the matrix isolated spectra of these molecules and subsequently to evaluate whether the method would prove sufficiently sensitive for the subsequent analysis of these malodorous substances in polluted atmospheres, and to compare the results with those already available from gas liquid chromatography and mass spectrometry. These results are discussed in chapter 8.In practice anomalous intensity variations were discovered in the spectrum of methylamine (chapter 4) which complicated the quantitative work. No such intensity variations were observed for ethylamine or ammonia (chapters 6 and 7). The abnormalities justified a thorough infrared and Raman spectroscopic analysis of the three molecules.Chapter 1 gives an outline of the project and introduces the matrix isolation technique.Chapters 2 and 3 deal with the experimental techniques employed for the infrared and Raman spectroscopic studies along with additional data analysing techniques.Chapter 4 presents the results and a complete spectral assignment for methylamine and methylamine-d2. These results are used in a normal coordinate analysis (chapter 5). The resulting force field is used to predict the spectrum of the methylarrdne-d^ molecule, enabling a more positive assignment to be made for thepreviously unobserved NI^ and ND2 twisting frequencies.In chapter 6 information concerning the conformational isomerism of ethylamine is obtained. Although there is some conflict between the infrared and Raman results for the CCN symmetric stretching vibration, the evidence is generally in favour of both conformers being present in argon and only the more stable trans conformer in nitrogen.The spectroscopic studies of ammonia in argon and nitrogen matrices are presented in chapter 7. Agreement is obtained with previous work for the argon matrix in the infrared, namely that the temperature dependence of the bands could be explained as being due to the rotational freedom of the molecule in the substitutional site. However, the Raman results are completely incompatible with the theory that relatively free rotation in the matrix site is occurring. Using a group theoretical treatment the results are explained, at least qualitatively, as due to a constrained orientational motion rather than a rotational one.Further information was obtained concerning the dimer species of ammonia in the matrices. The evidence leads to the conclusion that the open chain dimer predominates in the argon matrix but that both open chain and cyclic dimers are present in reasonable quantities in the nitrogen matrix. A detailed assignment of the open chain dimer frequencies is presented

Detection of Babesia divergens in southern Norway by using an immunofluorescence antibody test in cow sera

<p>Abstract</p> <p>Background</p> <p>The incidence of bovine babesiosis, caused by <it>Babesia divergens </it>(Apicomplexa: Piroplasmida) has decreased markedly since the 1930 s, but may re-emerge as a consequence of climate change and changes in legislation and pasturing practices. This is a potentially serious disease, with both economical and animal welfare consequences. Therefore, there is a need to survey the distribution of <it>B. divergens</it>.</p> <p>Methods</p> <p>We tested sera from 306 healthy pastured cows from 24 farms along the southern Norwegian coast by using an indirect immunofluorescence IgG antibody test (IFAT). Fractions of seropositive cows were compared by calculating 95% CI.</p> <p>Results</p> <p>The results of this test showed that 27% of the sera were positive for <it>B. divergens </it>antibodies. The fraction of antibody-positive sera that we detected showed a two-humped distribution, with a high fraction of positives being found in municipalities in the western and eastern parts of the study area, while the municipalities between these areas had few or no positive serum samples.</p> <p>Conclusions</p> <p>Neither the farmers' observations nor the Norwegian Dairy Herd Recording System give an adequate picture of the distribution of bovine babesiosis. Serological testing of cows by using IFAT is a convenient way of screening for the presence of <it>B. divergens </it>in an area.</p

African Americans, Gentrification, and Neoliberal Urbanization: the Case of Fort Greene, Brooklyn

This article examines the gentrification of Fort Greene, which is located in the western part of black Brooklyn, one of the largest contiguous black urban areas in the USA. Between the late 1960s and 2003, gentrification in Fort Greene followed the patterns discovered by scholars of black neighborhoods; the gentrifying agents were almost exclusively black and gentrification as a process was largely bottom-up because entities interested in the production of space were mostly not involved. Since 2003, this has changed. Whites have been moving to Fort Greene in large numbers and will soon represent the numerical majority. Public and private interventions in and around Fort Greene have created a new top-down version of gentrification, which is facilitating this white influx. Existing black residential and commercial tenants are replaced and displaced in the name of urban economic development

Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials

AIMS/HYPOTHESIS: Delayed-release metformin (Metformin DR) was developed to maximise gut-based mechanisms of metformin action by targeting the drug to the ileum. Metformin DR was evaluated in two studies. Study 1 compared the bioavailability and effects on circulating glucose and gut hormones (glucagon-like peptide-1, peptide YY) of Metformin DR dosed twice-daily to twice-daily immediate-release metformin (Metformin IR). Study 2 compared the bioavailability and glycaemic effects of Metformin DR dosages of 1,000 mg once-daily in the morning, 1,000 mg once-daily in the evening, and 500 mg twice-daily. METHODS: Study 1 was a blinded, randomised, crossover study (three × 5 day treatment periods) of twice-daily 500 mg or 1,000 mg Metformin DR vs twice-daily 1,000 mg Metformin IR in 24 participants with type 2 diabetes conducted at two study sites (Celerion Inc.; Tempe, AZ, and Lincoln, NE, USA). Plasma glucose and gut hormones were assessed over 10.25 h at the start and end of each treatment period; plasma metformin was measured over 11 h at the end of each treatment period. Study 2 was a non-blinded, randomised, crossover study (three × 7 day treatment periods) of 1,000 mg Metformin DR once-daily in the morning, 1,000 mg Metformin DR once-daily in the evening, or 500 mg Metformin DR twice-daily in 26 participants with type 2 diabetes performed at a single study site (Celerion, Tempe, AZ). Plasma glucose was assessed over 24 h at the start and end of each treatment period, and plasma metformin was measured over 30 h at the end of each treatment period. Both studies implemented centrally generated computer-based randomisation using a 1:1:1 allocation ratio. RESULTS: A total of 24 randomised participants were included in study 1; of these, 19 completed the study and were included in the evaluable population. In the evaluable population, all treatments produced similar significant reductions in fasting glucose (median reduction range, −0.67 to −0.81 mmol/l across treatments) and postprandial glucose (Day 5 to baseline AUC(0–t) ratio = 0.9 for all three treatments) and increases in gut hormones (Day 5 to baseline AUC(0–t) ratio range: 1.6–1.9 for GLP-1 and 1.4–1.5 for PYY) despite an almost 60% reduction in systemic metformin exposure for 500 mg Metformin DR compared with Metformin IR. A total of 26 randomised participants were included in study 2: 24 had at least one dose of study medication and at least one post-dose pharmacokinetic/pharmacodynamic assessment and were included in the pharmacokinetic/pharmacodynamic intent-to-treat analysis; and 12 completed all treatment periods and were included in the evaluable population. In the evaluable population, Metformin DR administered once-daily in the morning had 28% (90% CI −16%, −39%) lower bioavailability (least squares mean ratio of metformin AUC(0–24)) compared with either once-daily in the evening or twice-daily, although the glucose-lowering effects were maintained. In both studies, adverse events were primarily gastrointestinal in nature, and indicated similar or improved tolerability for Metformin DR vs Metformin IR; there were no clinically meaningful differences in vital signs, physical examinations or laboratory values. CONCLUSIONS/INTERPRETATION: Dissociation of gut hormone release and glucose lowering from plasma metformin exposure provides strong supportive evidence for a distal small intestine-mediated mechanism of action. Directly targeting the ileum with Metformin DR once-daily in the morning may provide maximal metformin efficacy with lower doses and substantially reduce plasma exposure. Metformin DR may minimise the risk of lactic acidosis in those at increased risk from metformin therapy, such as individuals with renal impairment. TRIAL REGISTRATION: Clinicaltrials.gov NCT01677299, NCT01804842 FUNDING: This study was funded by Elcelyx Therapeutics Inc. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-016-3992-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.