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Biomedical subjects

L Schäfer

Publications and source records attributed to L Schäfer.

At least 19 recordsLinked to original sources

Calculation of the persistence length of a flexible polymer chain with short-range self-repulsion.

For a self-repelling polymer chain consisting of n segments we calculate the persistence length L (j,n), defined as the projection of the end-to-end vector on the direction of the j-th segment. This quantity shows some pronounced variation along the chain. Using the renormalization group and epsilon-expansion we establish the scaling form and calculate the scaling function to order epsilon 2. Asymptotically, the simple result L (j,n) approximately const [j(n-j)/n]2nu-1 emerges for dimension d = 3. Also away from the excluded-volume limit L (j,n) is found to behave very similar to the swelling factor of a chain of length j (n-j)/n. We carry through simulations which are found to be in good accord with our analytical results. For d = 2 both our and previous simulations as well as theoretical arguments suggest the existence of logarithmic anomalies.

Journal Article↗

Electrochemical advanced oxidation process using DiaChem electrodes.

The electrochemical advanced oxidation process (EAOP) using boron doped diamond (DiaChem, registered trademark of Condias GmbH) has been studied for wastewater treatment and drinking water disinfection. DiaChem electrodes consist of preferentially metallic base materials coated with a conductive polycrystalline diamond film by hot-filament chemical vapour deposition. They exhibit high overpotential for water electrolysis as well as high chemical inertness and extended lifetime. In particular the high overpotential for water decomposition opens the widest known electrochemical window, allowing the energy efficient production of hydroxyl radicals directly from aqueous solutions. The hydroxyl radicals on the other hand are effectively used for the oxidation of pollutants. The EAOP using DiaChem electrodes thus facilitates the direct and, if necessary, complete decomposition of even hazardous or persistent pollutants in different wastewaters. Current efficiencies of more than 90%, also without the use of additives for hydroxyl radical generation, have been demonstrated. Additionally, for drinking water preparation diamond electrodes facilitate disinfection with and without the support of chlorine.

Electrochemistry↗

The coherent scattering function of the reptation model: simulations compared to theory.

We present results of Monte Carlo simulations measuring the coherent structure function of a chain moving through an ordered lattice of fixed topological obstacles. Our computer experiments use chains up to 320 beads and cover a large range of wave vectors and a time range exceeding the reptation time. For additional information we also measured the coherent structure function of internal pieces of the chain. We compare our results i) to the predictions of the primitive chain model, ii) to an approximate form resulting from Rouse motion in a coiled tube, and iii) to our recent evaluation of the full reptation model. i) The primitive chain model can fit the data for times t < or approximately equal to 20T2, where T(2) is the Rouse time of the chain. Besides some phenomenological amplitude factor this fit involves the reptation time T(3) as a second fit parameter. For the chain lengths measured, the asymptotic behavior T3 approximately equal to N3 is not attained. ii) The model of Rouse motion in a tube, which we have criticized before on theoretical grounds, is shown to fail also on the purely phenomenological level. iii) Our evaluation of the full reptation model yields an excellent fit to the data for both total chains and internal pieces and for all wave vectors and all times, provided specific micro-structure effects of the MC dynamics are negligible. Such micro-structure effects show up for wave vectors of the order of the inverse segment size and enforce the introduction of some phenomenological, wave-vector-dependent prefactor. For the dynamics of the total chain our data analysis based on the full reptation model shows the importance of tube length fluctuations. Universal (Rouse-type) internal relaxation, however, is unimportant. It can be observed only in the form of the diffusive motion of a short central subchain in the tube. Finally, we present a fit formula which in a large range of wave vectors and chain lengths reproduces the numerical results of our theory for the scattering from the total chain.

Journal Article↗

Digital light microscopy: prerequisite for optimum contrast enhancement and increase of resolution.

Since the reproducible production of microscope objectives was enabled by the lens calculations of Ernst Abbe in 1872, various attempts have been made to further increase the resolution of light microscopes. Apart from the improvements on the optical side, especially the introduction of fluorescence methods, the use of digital cameras connected to computers have brought us close to the theoretical limits of optical resolution. Due to improved speed and memory capacity of modern computers mathematical methods can be applied to stored three-dimensional (3D) sequences of digital images which, in addition to just contrast and edge enhancement, may result in the case of real 3D deconvolution, even in the visualisation of structures beyond the theoretical limitations of light optical resolution.

Animals↗

Apoptotic responsiveness of the Ewing's sarcoma family of tumours to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).

We investigated the cytotoxic responsiveness of 40 cell lines derived from representatives of the Ewing's sarcoma family of tumours (ESFT), i.e., Ewing's sarcoma (ES), peripheral primitive neuroectodermal tumour (pPNET) and Askin tumour (AT), to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Incubation with TRAIL at 100 ng/ml induced cell death at 24 hr in 19 of 26 ES, 11 of 12 pPNET and 2 of 2 AT cell lines. Half-maximal cell death concentrations (IC(50) values) varied from 0.1 to 20 ng/ml. TRAIL displayed potent cytotoxic activity against freshly derived ESFT cell isolates. Cytotoxicity was associated with phosphatidylserine expression and internucleosomal DNA fragmentation, features characteristic of apoptosis. The apoptotic programme in the sensitive ESFT VH-64 cell line revealed TRAIL-induced activation of FLICE/MACH1 (caspase-8) and CPP32/Yama/apopain (caspase-3) and processing of the prototype caspase substrate poly(ADP-ribose) polymerase. In addition, TRAIL provoked a collapse of the mitochondrial transmembrane potential (DeltaPsi(m)), parallelled by a reduction in ATP levels and release of cytochrome c from mitochondria into the cytosol. Inhibition of caspase-8 and caspase-3 by zIETDfmk and zDEVDfmk, respectively, substantially prevented TRAIL-induced apoptosis. However, zIETDfmk, but not zDEVDfmk, reduced TRAIL-mediated DeltaPsi(m) dissipation, indicating that TRAIL causes mitochondrial dysfunction through caspase-8 acting upstream of mitochondria. While macromolecule synthesis inhibitors (actinomycin D, cycloheximide) augmented susceptibility to TRAIL in TRAIL-responsive cell lines, these agents did not render TRAIL-resistant cell lines susceptible to TRAIL. However, the proteasome inhibitor MG132 sensitised to TRAIL in resistant cell lines. Collectively, these results show that TRAIL initiates effective death in the vast majority (80%) of cell lines derived from ESFT. Since TRAIL provoked cell death in ESFT ex vivo, this cytokine may be a promising drug for the treatment of ESFT in vivo.

Adenosine Triphosphate↗

Theta-point behavior of diluted polymer solutions: can one observe the universal logarithmic corrections predicted by field theory?

In recent large-scale Monte Carlo simulations of various models of Theta-point polymers in three dimensions Grassberger and Hegger found logarithmic corrections to mean field theory with amplitudes much larger than the universal amplitudes of the leading logarithmic corrections calculated by Duplantier in the framework of tricritical O(n) field theory. To resolve this issue we calculate the universal subleading correction of field theory, which turns out to be of the same order of magnitude as the leading correction for all chain lengths available in present day simulations. Borel resummation of the renormalization group flow equations also shows the presence of such large corrections. This suggests that the published simulations did not reach the asymptotic regime. To further support this view, we present results of Monte Carlo simulations on a Domb-Joyce-like model of weakly interacting random walks. Again the results cannot be explained by keeping only the leading corrections, but are in fair accordance with our full theoretical result. The corrections found for the Domb-Joyce model are much smaller than those for other models, which clearly shows that the effective corrections of are not yet in the asymptotic regime. Altogether, our findings show that the existing simulations of Theta polymers are compatible with tricritical field theory, since the crossover to the asymptotic regime is very slow. Similar results were found earlier for self-avoiding walks at their upper critical dimension d(c)=4.

Journal Article↗

Overlapping anomeric effects in a sucrose analogue.

Previous calculations with the molecular mechanics program MM3 gave unusually high energies (as much as 5.5 kcal/mol) for sucrosyl geometries found in single-crystal diffraction studies of oligosaccharides. Comparable MM3 energies for observed interresidue linkage conformations of disaccharides such as maltose and cellobiose are all within 2.8 kcal/mol. These results suggest that some energies calculated by MM3 for the linkage between anomeric centers of a pyranose ring and a furanose ring are too high. In the present paper, ab initio calculations at the 4-21G level and MM3 were used to study the conformational energies and geometry of a sucrose analogue, tetrahydro-2-[(tetrahydro-2-furanyl)oxy]-2H-pyran. The range of energies of the observed structures was substantially reduced (to 2.4 kcal/mol) with the 4-21G calculations for the analogue despite an increase for the analogue (to 7.5 kcal/mol) based on new MM3 calculations. Besides the improved energy values, the 4-21G calculations also reproduced the observed variations in the endocyclic C-O bond lengths better than did MM3.

Carbohydrate Conformation↗

Supplementation with evening primrose oil in atopic dermatitis: effect on fatty acids in neutrophils and epidermis.

We investigated the effect of oral supplementation with evening primrose oil, containing 72% linoleic acid (18:2n-6) and 10% gamma-linolenic acid (18:3n-6), on the epidermal and neutrophil phospholipid fatty acid composition in 15 patients with atopic dermatitis (AD). Three different dose levels, 4, 8 and 12 capsules per day containing 0.5 g oil, were given to three groups of patients. The only n-6 fatty acid showing a significant (p less than 0.05) dose-related increase was dihomo-gamma-linolenic acid (20:3n-6) in neutrophil phospholipids. The highest dose increased dihomo-gamma-linolenic acid by 45% in neutrophil phospholipids, by 46% in lesion-free epidermal phosphatidylcholine, and by 15% in lesion-free epidermal phosphatidylethanolamine. In both lesional and lesion-free epidermis, supplementation resulted in a rise in the ratio between n-6 and monounsaturated fatty acids, reaching significance (p less than 0.05) in lesional epidermis. This study shows that moderate and favorable fatty acid changes can be obtained in the epidermis of AD patients, when given 6 g per day of oil rich in n-6 fatty acids. The abnormal lipid and fatty acid pattern of the atopic epidermis may be involved in the pathogenesis of the disease, and should therefore be the target for future therapeutic approaches with fatty acid supplements.

Adult↗

[Correspondence of mammographic and pathological-anatomical tumor extent in breast cancer].

Pre-operative mammograms and exact information on the pathological-anatomical extent of the tumour were available in 198 patients with carcinoma of the breast. The tumour as seen on the mammogram was measured and compared with the histological information. Five of the 198 carcinomas (2 1/2%) could not be seen on the mammogram. In 69.7% of cases, mammography was suspicious of a carcinoma and in 27.8% a lesion was found that required further investigation. In 67.7%, the mammographic and pathological tumour extent agreed within 3 mm. In 18.2% the tumour appeared more than 3 mm greater, and in 9.6% more than 3 mm smaller than real size; the error was greater than 30 mm in only 3.2%.

Adult↗

Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis.

Atopic dermatitis is an inflammatory skin disease characterized by dryness and itch of the skin. In this study, we measured the phospholipid content and the fatty acid pattern of lesional and lesion-free epidermal keratome biopsies on 15 patients. For comparison, epidermal biopsies were obtained from healthy individuals undergoing plastic surgery. The phospholipid content of atopic epidermis was nearly twice as high as in healthy epidermis. Monounsaturated fatty acids in the phosphoglycerides were significantly increased (p less than 0.001) and n-6 fatty acids were significantly decreased (p less than 0.001) in lesional atopic epidermis compared to lesion-free epidermis. The content of esterified arachidonic acid in phosphatidylcholine from lesional epidermis was only 49% of that found in healthy epidermis (p less than 0.001). The content of free arachidonic acid was 47% higher (p less than 0.05), whereas the content of free long-chain saturated fatty acids was decreased by 29% (p less than 0.01), in lesional compared to lesion-free atopic epidermis. The disease severity, calculated as an arbitrary index, correlated inversely with the n-6 fatty acid content of lesion-free atopic epidermis (r = -0.89, p less than 0.001). Our findings suggest that atopic epidermis is characterized by an increased activity of phospholipase A2 and an incomplete transformation of phospholipids into other lipid classes.

Adult↗

Reduced neutrophil LTB4 release in atopic dermatitis patients despite normal fatty acid composition.

Propositions about an abnormal fatty acid metabolism in atopic dermatitis patients prompted us to compare the phospholipid fatty acid composition and LTB4 release of neutrophils from 15 atopic dermatitis patients, as well as the adipose tissue triglyceride fatty acid composition, to that of 15 healthy controls matched by age, gender, and smoking habits. We found no differences in the tissue fatty acid composition between the two groups. The release of leukotriene B4 from Ca-ionophore-stimulated neutrophils in patients was on the average only 42% (p less than 0.001) of that measured in the control group, despite the very similar arachidonic acid contents of these cells. Our study does not support the assumption of an abnormal fatty acid desaturation in atopic dermatitis patients. Rather, the capacity to release and/or convert arachidonic acid into leukotrienes in neutrophils appears to be affected by this disease.

Adipose Tissue↗

Lipid peroxidation and antioxidant supplementation in old age.

An age-related rise in blood lipid peroxides measured by the thiobarbituric acid (TBA) method has been reported in several studies. Our study was designed to investigate whether this could be attributed to antioxidant deficiencies in aged individuals. We therefore measured the TBA-value of young and old women and related this to vitamin E and selenium status and the fatty acid composition, triglyceride and cholesterol content of platelet-poor plasma. A significant difference (p less than 0.001) between young and old women in the plasma TBA-value and the plasma lipid parameters was found. Old women had a lower selenium status than the young women (p less than 0.01), but their vitamin E status was fully adequate. Only the lipid parameters correlated significantly (p less than 0.001) with the TBA-value. In a 3-month placebo-controlled supplementation trial with vitamin E and selenium, the plasma TBA-value of the old women did not change. This study shows that the TBA-value of plasma is primarily determined by the fatty acid content and is not influenced by antioxidant supplementation in healthy individuals. The question of the sensitivity of the TBA-test is discussed.

Adult↗

Subcutaneous adipose-tissue fatty acids and vitamin E in humans: relation to diet and sampling site.

The influence of diet and sampling site on subcutaneous adipose-tissue fatty acid composition and vitamin E content was examined in 20 healthy subjects. A dietary history and adipose-tissue biopsies from the buttock were obtained from 14 individuals. In another six individuals, samples were taken from both waist and buttock. The relative dietary intake of both polyunsaturated and saturated fatty acids correlated with the relative content in adipose tissue (r = 0.6, p = 0.02). Adipose-tissue vitamin E was strongly associated with dietary intake (r = 0.76, p = 0.004). The content of n - 3 (omega-3) fatty acids in adipose tissue was shown to influence adipose-tissue vitamin E negatively. Waist and buttock fat differed (p less than 0.05) with regard to fatty acid composition whereas no systematic variation was seen in the vitamin E content. The use of adipose-tissue biopsies in epidemiologic studies as measures of the habitual relative intake of fatty acids and vitamin E is suggested.

Adipose Tissue↗

Adipose tissue levels of fatty acids and tocopherol in young and old women.

Tocopherol concentration and fatty acid composition were determined in samples of subcutaneous adipose tissue from 33 young and 28 old women. Young women exhibited more saturated fatty acids and less monounsaturated fatty acids than old women (p less than 0.01). Adipose tissue tocopherol correlated with plasma tocopherol, with r = 0.49 and p less than 0.01, when the data for young and old were combined. A negative association was found between adipose tissue tocopherol and the n-3/n-6 fatty acid ratio in the old women (r = 0.42; p less than 0.05), suggesting that the tocopherol content of adipose tissue is determined not only by the intake of the nutrient but also by the tissue fatty acid composition.

Adipose Tissue↗