The influence of depressive symptoms on smoking cessation among African Americans in a randomized trial of bupropion.

The influence of depressive symptoms on smoking cessation was examined among 600 African American smokers who participated in a randomized, placebo-controlled trial of sustained-release bupropion hydrochloride. Depressive symptoms were assessed at baseline, at week 6 (end of treatment), and at 6-month follow-up. The study examined three separate questions: (a) Whether depressive symptom levels were related to smoking cessation, (b) whether bupropion was more effective for smokers who had higher depressive symptoms at baseline (i.e., a moderator model), and (c) whether changes in depressive symptoms would account for the efficacy of bupropion for smoking cessation (i.e., a mediator model). Depressive symptoms at baseline were not predictive of cessation; however, increases in depressive symptoms from baseline predicted reduced cessation at the end of treatment, and higher depressive symptoms at week 6 and month 6 were associated with a reduced likelihood of smoking cessation at those time points. The moderator model was not supported, but the mediation analyses indicated that alleviation of depressive symptoms partly accounted for bupropion-assisted smoking cessation at end of treatment. Results extend prior findings to African American smokers and suggest that clinicians consider increases in depressive symptoms after quitting rather than baseline depressive symptoms in predicting risk of treatment failure. Results also suggest that even though bupropion may facilitate cessation in part by reducing depressive symptoms, it appears to be no more effective for more depressed smokers, and that mechanisms other than depressive symptom alleviation account for most of its efficacy.     

Effect of incident angle in spectral ellipsometry on composition control during molecular beam epitaxial growth of HgCdTe

The effect of incident angle in spectral ellipsometry (SE) on composition control of Hg_1−xCd_xTe grown by molecular beam epitaxy (MBE) was investigated. Although a small uncertainty in the incident angle tends to have a significant impact on the ellipsometric data, and therefore the composition data, it was found that the incident angle uncertainty could be corrected in the SE model calculation, resulting in an “optimized” incident angle that would give the best fit between measured and calculated ellipsometric data. Experimental data supporting this simple corrective or optimization procedure for the incident angle are presented.     

Impact of analytical bias in metabonomic studies of human blood serum and plasma

Concurrent with the explosion in the number of publications reporting biomarker discovery by profiling technologies, such as proteomics and pattern recognition, has been the increase in evidence highlighting the susceptibility of these approaches to analytical and experimental bias. The work presented here addresses these timely issues by delivering a detailed characterization of the effect of common sources of bias in clinical studies on serum and plasma profiles generated by a key technology in metabonomics, NMR spectroscopy. Specifically, differences in composition when blood samples were collected onto and in the absence of ice, over a series of serum-clot contact times, the stability of NMR-prepared samples over time and the effect on the metabolic profile of freeze-thawing were examined. While differences between individuals were far greater than variation from any other experimental factor, each of the conditions examined did cause slight alterations to the NMR profile that could produce a systematic bias. Variation due to clotting time caused changes in energy metabolites, which were delayed by ice with no other spectral effects. Room-temperature stability and hence NMR spectral repeatability were high (<1% intrasample variation). Higher molecular weight species such as lipoproteins were more susceptible to the variations present in the examined factors. These observations have implications for profiling study design, and hence, our results form a new and valuable resource for those attempting clinical metabolic profiling, for regulatory agencies involved in the licensing of clinical tests and in the generation of international reporting standards for metabonomics.     

Correlation between protein binding strength on immobilized metal affinity chromatography and the histidine-related protein surface structure

Immobilized metal affinity chromatography (IMAC) was investigated for its ability to characterize the histidine-related surface structure of a protein, that is, a histidine residue's surface accessibility and its potential involvement in intramolecular interactions. T4 lysozyme was chosen as the model protein. Seven amino acid sites were selected on the basis of their relative surface accessibility, and they were substituted with histidine via site-directed protein mutagenesis to generate seven T4 lysozyme variants, each containing only one histidine residue on its surface, with various surface accessibility. IMAC was then used to experimentally quantify the interaction of each lysozyme variant with immobilized copper ions. A direct correlation was shown between the protein binding affinity and the surface accessibility of the histidine residue. Of all the lysozyme variants, K83H and K147H showed unusually low binding strength, as compared with variants having a histidine residue with a similar surface accessibility. However, with the aid of molecular modeling, their relatively low binding affinities were predicted to be the result of the involvement of the histidine residue in intramolecular interactions. In contrast to previously reported results, our results showed that lysozyme still binds to the IMAC column, even if its histidine residue is involved in intramolecular bonding, such as a hydrogen bond, albeit at reduced strength, as compared with the variant containing a histidine residue with a similar surface accessibility.     

Cell lineage tracing in the developing enteric nervous system: superstars revealed by experiment and simulation

Cell lineage tracing is a powerful tool for understanding how proliferation and differentiation of individual cells contribute to population behaviour. In the developing enteric nervous system (ENS), enteric neural crest (ENC) cells move and undergo massive population expansion by cell division within self-growing mesenchymal tissue. We show that single ENC cells labelled to follow clonality in the intestine reveal extraordinary and unpredictable variation in number and position of descendant cells, even though ENS development is highly predictable at the population level. We use an agent-based model to simulate ENC colonization and obtain agent lineage tracing data, which we analyse using econometric data analysis tools. In all realizations, a small proportion of identical initial agents accounts for a substantial proportion of the total final agent population. We term these individuals superstars. Their existence is consistent across individual realizations and is robust to changes in model parameters. This inequality of outcome is amplified at elevated proliferation rate. The experiments and model suggest that stochastic competition for resources is an important concept when understanding biological processes which feature high levels of cell proliferation. The results have implications for cell-fate processes in the ENS.     

Digital Doppler measurement with spacecraft

Digital and analog phase-locked loop (PLL) receivers were operated in parallel, each tracking the residual carrier from a spacecraft. The PLL tracked the downlink carrier and measured its instantaneous phase. This information, combined with a knowledge of the uplink carrier and the transponder ratio, permitted the computation of a Doppler observable. In this way, two separate Doppler measurements were obtained for one observation window. The two receivers agreed on the magnitude of the Doppler effect to within 1 mHz. There was less jitter on the data from the digital receiver. This was due to its smaller noise bandwidth. The demonstration and its results are described     

Dietary vitamin E supplementation inhibits thrombin-induced platelet aggregation, but not monocyte adhesiveness, in patients with hypercholesterolaemia

Advanced age is an established risk factor for gastrointestinal toxicity of nonsteroidal antiinflammatory drugs, and the duration of use of these agents in elderly patients should be kept as short as possible. A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of misoprostol in preventing gastrointestinal toxicity in elderly patients (> or = 65 years) given nonsteroidal antiinflammatory agents for no more than ten days. Patients who were to receive a nonsteroidal antiinflammatory agent for ten days to treat an acute rheumatic condition were randomly allocated to treatment with either a placebo or misoprostol in a dose of 200 micrograms bid. The primary efficacy criterion was the result of a gastroduodenal endoscopic evaluation done on day 10. The outcome of the rheumatic condition, changes in serum creatinine levels, and clinical safety were also evaluated. The study population included 208 subjects with a mean age of 81.4 +/- 6.4 years, of whom 81.3% were women. The misoprostol group (n = 104) and the placebo group (n = 104) were comparable at baseline. The incidence of endoscopically visible gastric lesions after ten days of nonsteroidal antiinflammatory drug therapy was significantly lower in the misoprostol group (25%) than in the placebo group (43%) (P = 0.001). In contrast, no statistically significant difference was found for the incidence of duodenal lesions between the two groups. The incidence of gastroduodenal ulcers was significantly lower (P < 0.021) in the misoprostol group (4.1%) than in the placebo group (13.5%). Changes in serum creatinine levels on day 10 versus baseline were similar in the two groups. The nonsteroidal antiinflammatory drug was well tolerated clinically when given alone or in combination with misoprostol.