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61.
Summary The hard palates of 150 female albino rats of the Sprague-Dawley strain were painted 3 times a week either with the fat-soluble carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) for 11 months with inhibited secretion of saliva or with the water-soluble carcinogen 4-nitrochinoline N-oxide (4NQO) for 8 months with intact salivary secretion. Specimens were taken regularly from the mucosa of the hard palate, and the content of lipids in the epithelium was studied histochemically and biochemically during the carcinogenesis.Changes in the lipid content could be observed histochemically as there was a focal loss of lipid stainability in the epithelium during the more advanced stages of carcinogenesis with severe epithelial dysplasia, carcinoma in situ and early invasive carcinoma.The biochemical method used (TLC) could not, however, verify the histologically observed changes in the lipid content of the epithelium, probably because the changes were very local.The investigations have been performed with financial support from Maggie Stephens Foundation, Colgate-Palmolive Limited and from the Swedish Dental Society. 相似文献
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Carl Rafferty Kjell Johnson Jim O'Mahony Barbara Burgoyne Rosemary Rea Karin M. Balss 《Biotechnology progress》2020,36(4):e2977
The Food and Drug Administration (FDA) initiative of Process Analytical Technology (PAT) encourages the monitoring of biopharmaceutical manufacturing processes by innovative solutions. Raman spectroscopy and the chemometric modeling tool partial least squares (PLS) have been applied to this aim for monitoring cell culture process variables. This study compares the chemometric modeling methods of Support Vector Machine radial (SVMr), Random Forests (RF), and Cubist to the commonly used linear PLS model for predicting cell culture components—glucose, lactate, and ammonia. This research is performed to assess whether the use of PLS as standard practice is justified for chemometric modeling of Raman spectroscopy and cell culture data. Model development data from five small-scale bioreactors (2 × 1 L and 3 × 5 L) using two Chinese hamster ovary (CHO) cell lines were used to predict against a manufacturing scale bioreactor (2,000 L). Analysis demonstrated that Cubist predictive models were better for average performance over PLS, SVMr, and RF for glucose, lactate, and ammonia. The root mean square error of prediction (RMSEP) of Cubist modeling was acceptable for the process concentration ranges of glucose (1.437 mM), lactate (2.0 mM), and ammonia (0.819 mM). Interpretation of variable importance (VI) results theorizes the potential advantages of Cubist modeling in avoiding interference of Raman spectral peaks. Predictors/Raman wavenumbers (cm−1) of interest for individual variables are X1139–X1141 for glucose, X846–X849 for lactate, and X2941–X2943 for ammonia. These results demonstrate that other beneficial chemometric models are available for use in monitoring cell culture with Raman spectroscopy. 相似文献
66.
Alexander G. Georgiev Jesper Johansen Vidhya D. Ramanathan Yves Y. Sere Christopher T. Beh Anant K. Menon 《Traffic (Copenhagen, Denmark)》2013,14(8):912-921
The pan‐eukaryotic endoplasmic reticulum (ER) membrane protein Arv1 has been suggested to play a role in intracellular sterol transport. We tested this proposal by comparing sterol traffic in wild‐type and Arv1‐deficient Saccharomyces cerevisiae. We used fluorescence microscopy to track the retrograde movement of exogenously supplied dehydroergosterol (DHE) from the plasma membrane (PM) to the ER and lipid droplets and high performance liquid chromatography to quantify, in parallel, the transport‐coupled formation of DHE esters. Metabolic labeling and subcellular fractionation were used to assay anterograde transport of ergosterol from the ER to the PM. We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. Instead, our results indicate differences in ER morphology and the organization of the PM lipid bilayer between wild‐type and arv1Δ cells suggesting a distinct role for Arv1 in membrane homeostasis. In arv1Δ cells, specific defects affecting single C‐terminal transmembrane domain proteins suggest that Arv1 might regulate membrane insertion of tail‐anchored proteins involved in membrane homoeostasis . 相似文献
67.
Long‐term phenology monitoring has documented numerous examples of changing flowering dates during the last century. A pivotal question is whether these phenological responses are adaptive or not under directionally changing climatic conditions. We use a classic dynamic growth model for annual plants, based on optimal control theory, to find the fitness‐maximizing flowering time, defined as the switching time from vegetative to reproductive growth. In a typical scenario of global warming, with advanced growing season and increased productivity, optimal flowering time advances less than the start of the growing season. Interestingly, increased temporal spread in production over the season may either advance or delay the optimal flowering time depending on overall productivity or season length. We identify situations where large phenological changes are necessary for flowering time to remain optimal. Such changes also indicate changed selection pressures. In other situations, the model predicts advanced phenology on a calendar scale, but no selection for early flowering in relation to the start of the season. We also show that the optimum is more sensitive to increased productivity when productivity is low than when productivity is high. All our results are derived using a general, graphical method to calculate the optimal flowering time applicable for a large range of shapes of the seasonal production curve. The model can thus explain apparent maladaptation in phenological responses in a multitude of scenarios of climate change. We conclude that taking energy allocation trade‐offs and appropriate time scales into account is critical when interpreting phenological patterns. 相似文献
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Kristin Blidberg Lena Palmberg Anna James Bo Billing Elisabeth Henriksson Ann-Sofie Lantz Kjell Larsson Barbro Dahlén 《Respiratory research》2013,14(1):47
Background
The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.Methods
Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included. Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162). Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).Results
Expression of CD11b was increased on circulating neutrophils from smokers with COPD. It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05). In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).Conclusions
Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers. 相似文献69.
Britt-Marie Sundblad Sven-Arne Jansson Lennarth Nystr?m Peter Arvidsson Bo Lundb?ck Kjell Larsson 《PloS one》2013,8(12)
Background
Little is known about the management of patients suffering from chronic obstructive pulmonary disease (COPD) during the last years of life. The aim of the study was to describe how management of COPD is performed in Sweden during the last two years of life.Methods
From the nationwide Cause of Death register all individuals with COPD as the underlying cause of death during two years were identified in one sparsely and one densely populated area of Sweden. Data were collected from medical records using a pre-defined protocol, especially developed for this purpose.Results
Of 822 individuals with COPD as underlying cause of death, medical records from 729 were available. The COPD diagnosis was based on lung function measurements in approximately half of the patients and median age at COPD diagnosis was 74 years (range 34-95). Women died at younger age, median 78 years (range 52-96) than did men (80 years (51-99)). The median survival time from diagnosis to death was 6 years in men and women in both areas. Among women and men 8.3% and 4.3% were never smokers, respectively. The structure of COPD management differed between the two areas, with utilization of physiotherapists, dieticians and working therapists being more used in the northern area, likely because of differences in accessibility to care institutions.Conclusions
In Sweden COPD is mostly diagnosed late in life and often not verified by lung function measurements. Opposite to the general population, women with COPD die at a lower age than men. 相似文献70.