george gert - Academia.edu (original) (raw)
Papers by george gert
European Biophysics Journal With Biophysics Letters, 2000
Experimental evidence supporting the hypothesis of gel-liquid crystalline phase coexistence in th... more Experimental evidence supporting the hypothesis of gel-liquid crystalline phase coexistence in the stable ripple phase of diacylphosphatidylcholines has been obtained from time-resolved X-ray small- (SAXS) and wide-angle diffraction (WAXS) in the millisecond to second time domain. The pretransition of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) exhibits a thin lamellar liquid crystalline intermediate phase (designated Lα*) if driven far away from equilibrium by an infrared temperature jump (T-jump) technique. The findings can be described by a two-step model. (1) Instantaneously with the T-jump, an anomalously thin lamellar liquid crystalline intermediate phase (d = 5.6–5.8 nm) forms, coexisting with the original gel-phase Lβ′. Within the first seconds, the lamellar repeat distance of the intermediate increases to a value of about 6.7 nm. A closer examination of these kinetics reveals two relaxation components: a fast process, proceeding within tenths of a second, and a slow process, on the time scale of a few seconds. (2) Finally, both the liquid crystalline and the gel-phase relax into the stable ripple phase Pβ′. The total process time of the transition is nearly independent of the addition of NaCl, but varies strongly with the chain length of the lecithin species.
International Urology and Nephrology
Introduction Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic t... more Introduction Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic therapies. The aim of the present study was to identify differences between patients on oral antidiabetic drug therapy or insulin substitution or diet therapy alone during their first year of hemodialysis. Patients and methods Sixty-four type 2 diabetic patients who had started hemodialysis (HD) at our dialysis center between 2003 and 2007 were included in the study. Kidney-transplanted patients (n = 1) and those with chronic infectious or malignant diseases (n = 4) were excluded. Patients were divided into three groups according to their antidiabetic therapy: group 1 consisted of patients on oral antidiabetic drug therapy (n = 12), group 2 of those on insulin therapy (n = 42), and group 3 of those being treated with diet alone (n = 10). At the start of HD and 12 months later, we measured fasting plasma glucose (FPG), HbA1c, the incidence of hypoglycemia (n/patient/month), cholesterol, triglycerides, body weight, and insulin requirements in the insulin-treated group. C-peptide was only measured at the start of dialysis. We evaluated changes in antidiabetic therapy during the first year on dialysis, and the prevalence of vascular disease in each group at the start of HD. Results FPG and HbA1c values were similar in all groups at the start of HD and after 1 year. Hypoglycemia occurred more frequently in insulin-treated patients; however, the difference was not significant. Cholesterol levels were similar in all groups, whereas triglycerides were significantly lower in insulin-treated patients (138 ± 28 vs. 176 ± 46 mg/dl; P < 0.05). Body weight was similar in all groups. No significant change in body weight was observed in any group after 12 months on dialysis. At the start of HD, C-peptide levels were lower in insulin-treated patients than in the other groups (1.8 ± 0.9 ng/ml vs. 2.2 ± 1.1 and 2.4 ± 1.1 ng/ml; P < 0.05). During the first 12 months on HD, two patients from group 1 were shifted to group 3 (diet alone), while four patients could reduce their drug dosage (33%). However, two subjects became insulin-dependent. In group 2, insulin therapy could be terminated in two cases, while the insulin dose could be reduced in 20 patients (48%). In group 3, one patient was switched to oral antidiabetic therapy. The prevalence of vascular disease was slightly higher in group 3 (NS). Conclusion Within 1 year after the start of HD, the dose of sulfonylurea as well as insulin could be reduced in a large majority of patients. Metabolic control was similar in all groups. Only triglycerides were significantly lower in group 2. The frequency of hypoglycemia and the prevalence of vascular disease were just slightly higher in the group on insulin therapy.
Comprehensive catalog of European biobanks
Nature Biotechnology, 2011
Biobanks are well-organized resources comprising biological samples and associated information th... more Biobanks are well-organized resources comprising biological samples and associated information that are accessible to scientific investigation 1, 2. They have become a key element for research involving human genetic or genomic and proteomic information in ...
Breast Cancer Research and Treatment, 1997
Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surroundin... more Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surrounding neoplastic cells, and are believed to be induced by paracrine stimulation. Such stimulation, by the local release of angiogenic factors, is also responsible for the induction of new capillary blood vessels, a crucial aspect of tumor growth and metastasis. We have here compared the expression of a matrix metalloproteinase, stromelysin-3 (ST3), with the distribution of tumor microvessels in invasive breast carcinomas. The highest level of ST3 mRNA in each tumor was recorded and compared to the highest microvessel density. No correlation between these two parameters was observed by analysis of 63 tumors. Detailed examination of 19 individual tumors did not reveal any correlation between the distribution of ST3 mRNA and microvessels. In the material studied here, ST3 expression was observed to correlate with long-term survival of the patients, whereas microvessel density did not correlate.
The European tracking network
The GPS phase observable is well known to be subject to a number of errors, the most common of wh... more The GPS phase observable is well known to be subject to a number of errors, the most common of which is the so-called cycle slip. A cycle slip occurs when the receiver momentarily loses lock on a satellite, resulting in an error in the integer part of the phase observable of one or more cycles. It is essential to locate such errors and, if possible, repair them by adding back the appropriate number of cycles. A number of strategies are available. Here they are reviewed and a new strategy based on data collected at a single station only is presented. The new strategy has been implemented for the Trimble 4000S system and a computer program that can run on a microcomputer produced. This program can be used in the field to check the quality of GPS phase data before leaving the observing site.
Biophysical Journal, 1998
The existence of two different M-state structures in the photocycle of the bacteriorhodopsin muta... more The existence of two different M-state structures in the photocycle of the bacteriorhodopsin mutant ASP38ARG was proved. At pH 6.7 (0 to −6°C) a spectroscopic M intermediate (M1) that does not differ significantly in its tertiary structure from the light-adapted ground state accumulates under illumination. At pH > 9 another state (M2), characterized by additional pronounced changes in the Fourier transform infrared difference spectrum in the region of the amide I and II bands, accumulates. The M2 intermediate trapped at pH 9.6 displays the same changes in the x-ray diffraction intensities under continuous illumination as previously described for x-ray experiments with the mutant ASP96ASN. These observations indicate that in this mutant the altered charge distribution at neutral pH controls the tertiary structural changes that seem to be necessary for proton translocation.
Hairy Cell Leukaemia: Surface Markers and Functional Capacities of the Leukaemic Cells Analysed in Eight Patients
British Journal of Haematology, 1979
Summary. In eight patients with hairy cell leukaemia (HCL) peripheral blood cells and in two pati... more Summary. In eight patients with hairy cell leukaemia (HCL) peripheral blood cells and in two patients also spleen cells were analysed for surface markers and functional capacities. Only cells containing the tartrate resistant isoenzyme 5 of the acid phosphatase were considered. Hairy cells (HC) of all patients were found to adhere spontaneously to glass and plastic surfaces and to spread after adherence like monocytes. They ingested latex particles of more than 1 μm diameter, but, in contrast to monocytes, did not phagocytose erythrocytes sensitized either by IgM or by IgG antibodies. HC of all patients bore Fc-receptors with a high binding affinity for aggregated IgG. Using 125I-labelled F(ab′)2-fragments of monospecific antibodies in autoradiography, only one light chain type was detected on HC of individual patients. In four patients μ- and δ-chains were simultaneously expressed on HC, whereas in two patients only γ-chains and in one case only μ-chains were observed on HC. One patient showed a combination of γ- and δ-chains on his HC. A great variation in density of surface immunoglobulins of HC was observed within individual patients. After removal by capping, surface immunoglobulin reappeared on HC during cell culture, but more slowly than on normal B-lymphocytes. As shown in two patients by internal labelling, HC secreted immunoglobulin light chains, but no heavy chains. On the basis of these findings the classification of HC as belonging to the B-cell lineage, rather than to the monocytic lineage, seems to be justified.
MOVEMENT Modular Versatile Mobility Enhancement System
Although powered wheelchairs provide a well established solution for severely impaired persons th... more Although powered wheelchairs provide a well established solution for severely impaired persons they do not cover all needs regarding mobility of people with impairment. In the course of the EC funded research project MOVEMENT a novel approach for a highly adaptable and modular mobility enhancement system is targeted to cover additional user needs. A system consisting of a robotic platform and several dockable application modules is developed that additionally provides assistance for the driving process itself to the user or even takes over the complete driving autonomously. The project also includes development of new solutions for navigation of mobile robot systems including a "low-cost" sensor system as well as adaptable HMI components. This paper describes the concept and the first prototyping results.
Background. Adynamic bone disease was recently described to be increasingly prevalent in the dial... more Background. Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease. Methods. In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range. Results. In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being < 27 U/litre for the bone isoenzyme of alkaline phosphatase, ^ 14 ug/litre for osteocalcin and ^ 150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease.
Protein Science, 1992
The availability of fast and robust algorithms for protein structure comparison provides an oppor... more The availability of fast and robust algorithms for protein structure comparison provides an opportunity to produce a database of three-dimensional comparisons, called families of structurally similar proteins (FSSP). The database currently contains an extended structural family for each of 154 representative (below 30% sequence identity) protein chains. Each data set contains: the search structure; all its relatives with 70–30% sequence identity, aligned structurally; and all other proteins from the representative set that contain substructures significantly similar to the search structure. Very close relatives (above 70% sequence identity) rarely have significant structural differences and are excluded. The alignments of remote relatives are the result of pairwise all-against-all structural comparisons in the set of 154 representative protein chains. The comparisons were carried out with each of three novel automatic algorithms that cover different aspects of protein structure similarity. The user of the database has the choice between strict rigid-body comparisons and comparisons that take into account interdomain motion or geometrical distortions; and, between comparisons that require strictly sequential ordering of segments and comparisons, which allow altered topology of loop connections or chain reversals. The data sets report the structurally equivalent residues in the form of a multiple alignment and as a list of matching fragments to facilitate inspection by three-dimensional graphics. If substructures are ignored, the result is a database of structure alignments of full-length proteins, including those in the twilight zone of sequence similarity. The database makes explicitly visible architectural similarities in the known part of the universe of protein folds and may be useful for understanding protein folding and for extracting structural modules for protein design. The data sets are available via Internet.
European Biophysics Journal With Biophysics Letters, 2000
Experimental evidence supporting the hypothesis of gel-liquid crystalline phase coexistence in th... more Experimental evidence supporting the hypothesis of gel-liquid crystalline phase coexistence in the stable ripple phase of diacylphosphatidylcholines has been obtained from time-resolved X-ray small- (SAXS) and wide-angle diffraction (WAXS) in the millisecond to second time domain. The pretransition of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) exhibits a thin lamellar liquid crystalline intermediate phase (designated Lα*) if driven far away from equilibrium by an infrared temperature jump (T-jump) technique. The findings can be described by a two-step model. (1) Instantaneously with the T-jump, an anomalously thin lamellar liquid crystalline intermediate phase (d = 5.6–5.8 nm) forms, coexisting with the original gel-phase Lβ′. Within the first seconds, the lamellar repeat distance of the intermediate increases to a value of about 6.7 nm. A closer examination of these kinetics reveals two relaxation components: a fast process, proceeding within tenths of a second, and a slow process, on the time scale of a few seconds. (2) Finally, both the liquid crystalline and the gel-phase relax into the stable ripple phase Pβ′. The total process time of the transition is nearly independent of the addition of NaCl, but varies strongly with the chain length of the lecithin species.
International Urology and Nephrology
Introduction Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic t... more Introduction Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic therapies. The aim of the present study was to identify differences between patients on oral antidiabetic drug therapy or insulin substitution or diet therapy alone during their first year of hemodialysis. Patients and methods Sixty-four type 2 diabetic patients who had started hemodialysis (HD) at our dialysis center between 2003 and 2007 were included in the study. Kidney-transplanted patients (n = 1) and those with chronic infectious or malignant diseases (n = 4) were excluded. Patients were divided into three groups according to their antidiabetic therapy: group 1 consisted of patients on oral antidiabetic drug therapy (n = 12), group 2 of those on insulin therapy (n = 42), and group 3 of those being treated with diet alone (n = 10). At the start of HD and 12 months later, we measured fasting plasma glucose (FPG), HbA1c, the incidence of hypoglycemia (n/patient/month), cholesterol, triglycerides, body weight, and insulin requirements in the insulin-treated group. C-peptide was only measured at the start of dialysis. We evaluated changes in antidiabetic therapy during the first year on dialysis, and the prevalence of vascular disease in each group at the start of HD. Results FPG and HbA1c values were similar in all groups at the start of HD and after 1 year. Hypoglycemia occurred more frequently in insulin-treated patients; however, the difference was not significant. Cholesterol levels were similar in all groups, whereas triglycerides were significantly lower in insulin-treated patients (138 ± 28 vs. 176 ± 46 mg/dl; P < 0.05). Body weight was similar in all groups. No significant change in body weight was observed in any group after 12 months on dialysis. At the start of HD, C-peptide levels were lower in insulin-treated patients than in the other groups (1.8 ± 0.9 ng/ml vs. 2.2 ± 1.1 and 2.4 ± 1.1 ng/ml; P < 0.05). During the first 12 months on HD, two patients from group 1 were shifted to group 3 (diet alone), while four patients could reduce their drug dosage (33%). However, two subjects became insulin-dependent. In group 2, insulin therapy could be terminated in two cases, while the insulin dose could be reduced in 20 patients (48%). In group 3, one patient was switched to oral antidiabetic therapy. The prevalence of vascular disease was slightly higher in group 3 (NS). Conclusion Within 1 year after the start of HD, the dose of sulfonylurea as well as insulin could be reduced in a large majority of patients. Metabolic control was similar in all groups. Only triglycerides were significantly lower in group 2. The frequency of hypoglycemia and the prevalence of vascular disease were just slightly higher in the group on insulin therapy.
Comprehensive catalog of European biobanks
Nature Biotechnology, 2011
Biobanks are well-organized resources comprising biological samples and associated information th... more Biobanks are well-organized resources comprising biological samples and associated information that are accessible to scientific investigation 1, 2. They have become a key element for research involving human genetic or genomic and proteomic information in ...
Breast Cancer Research and Treatment, 1997
Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surroundin... more Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surrounding neoplastic cells, and are believed to be induced by paracrine stimulation. Such stimulation, by the local release of angiogenic factors, is also responsible for the induction of new capillary blood vessels, a crucial aspect of tumor growth and metastasis. We have here compared the expression of a matrix metalloproteinase, stromelysin-3 (ST3), with the distribution of tumor microvessels in invasive breast carcinomas. The highest level of ST3 mRNA in each tumor was recorded and compared to the highest microvessel density. No correlation between these two parameters was observed by analysis of 63 tumors. Detailed examination of 19 individual tumors did not reveal any correlation between the distribution of ST3 mRNA and microvessels. In the material studied here, ST3 expression was observed to correlate with long-term survival of the patients, whereas microvessel density did not correlate.
The European tracking network
The GPS phase observable is well known to be subject to a number of errors, the most common of wh... more The GPS phase observable is well known to be subject to a number of errors, the most common of which is the so-called cycle slip. A cycle slip occurs when the receiver momentarily loses lock on a satellite, resulting in an error in the integer part of the phase observable of one or more cycles. It is essential to locate such errors and, if possible, repair them by adding back the appropriate number of cycles. A number of strategies are available. Here they are reviewed and a new strategy based on data collected at a single station only is presented. The new strategy has been implemented for the Trimble 4000S system and a computer program that can run on a microcomputer produced. This program can be used in the field to check the quality of GPS phase data before leaving the observing site.
Biophysical Journal, 1998
The existence of two different M-state structures in the photocycle of the bacteriorhodopsin muta... more The existence of two different M-state structures in the photocycle of the bacteriorhodopsin mutant ASP38ARG was proved. At pH 6.7 (0 to −6°C) a spectroscopic M intermediate (M1) that does not differ significantly in its tertiary structure from the light-adapted ground state accumulates under illumination. At pH > 9 another state (M2), characterized by additional pronounced changes in the Fourier transform infrared difference spectrum in the region of the amide I and II bands, accumulates. The M2 intermediate trapped at pH 9.6 displays the same changes in the x-ray diffraction intensities under continuous illumination as previously described for x-ray experiments with the mutant ASP96ASN. These observations indicate that in this mutant the altered charge distribution at neutral pH controls the tertiary structural changes that seem to be necessary for proton translocation.
Hairy Cell Leukaemia: Surface Markers and Functional Capacities of the Leukaemic Cells Analysed in Eight Patients
British Journal of Haematology, 1979
Summary. In eight patients with hairy cell leukaemia (HCL) peripheral blood cells and in two pati... more Summary. In eight patients with hairy cell leukaemia (HCL) peripheral blood cells and in two patients also spleen cells were analysed for surface markers and functional capacities. Only cells containing the tartrate resistant isoenzyme 5 of the acid phosphatase were considered. Hairy cells (HC) of all patients were found to adhere spontaneously to glass and plastic surfaces and to spread after adherence like monocytes. They ingested latex particles of more than 1 μm diameter, but, in contrast to monocytes, did not phagocytose erythrocytes sensitized either by IgM or by IgG antibodies. HC of all patients bore Fc-receptors with a high binding affinity for aggregated IgG. Using 125I-labelled F(ab′)2-fragments of monospecific antibodies in autoradiography, only one light chain type was detected on HC of individual patients. In four patients μ- and δ-chains were simultaneously expressed on HC, whereas in two patients only γ-chains and in one case only μ-chains were observed on HC. One patient showed a combination of γ- and δ-chains on his HC. A great variation in density of surface immunoglobulins of HC was observed within individual patients. After removal by capping, surface immunoglobulin reappeared on HC during cell culture, but more slowly than on normal B-lymphocytes. As shown in two patients by internal labelling, HC secreted immunoglobulin light chains, but no heavy chains. On the basis of these findings the classification of HC as belonging to the B-cell lineage, rather than to the monocytic lineage, seems to be justified.
MOVEMENT Modular Versatile Mobility Enhancement System
Although powered wheelchairs provide a well established solution for severely impaired persons th... more Although powered wheelchairs provide a well established solution for severely impaired persons they do not cover all needs regarding mobility of people with impairment. In the course of the EC funded research project MOVEMENT a novel approach for a highly adaptable and modular mobility enhancement system is targeted to cover additional user needs. A system consisting of a robotic platform and several dockable application modules is developed that additionally provides assistance for the driving process itself to the user or even takes over the complete driving autonomously. The project also includes development of new solutions for navigation of mobile robot systems including a "low-cost" sensor system as well as adaptable HMI components. This paper describes the concept and the first prototyping results.
Background. Adynamic bone disease was recently described to be increasingly prevalent in the dial... more Background. Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease. Methods. In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range. Results. In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being < 27 U/litre for the bone isoenzyme of alkaline phosphatase, ^ 14 ug/litre for osteocalcin and ^ 150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease.
Protein Science, 1992
The availability of fast and robust algorithms for protein structure comparison provides an oppor... more The availability of fast and robust algorithms for protein structure comparison provides an opportunity to produce a database of three-dimensional comparisons, called families of structurally similar proteins (FSSP). The database currently contains an extended structural family for each of 154 representative (below 30% sequence identity) protein chains. Each data set contains: the search structure; all its relatives with 70–30% sequence identity, aligned structurally; and all other proteins from the representative set that contain substructures significantly similar to the search structure. Very close relatives (above 70% sequence identity) rarely have significant structural differences and are excluded. The alignments of remote relatives are the result of pairwise all-against-all structural comparisons in the set of 154 representative protein chains. The comparisons were carried out with each of three novel automatic algorithms that cover different aspects of protein structure similarity. The user of the database has the choice between strict rigid-body comparisons and comparisons that take into account interdomain motion or geometrical distortions; and, between comparisons that require strictly sequential ordering of segments and comparisons, which allow altered topology of loop connections or chain reversals. The data sets report the structurally equivalent residues in the form of a multiple alignment and as a list of matching fragments to facilitate inspection by three-dimensional graphics. If substructures are ignored, the result is a database of structure alignments of full-length proteins, including those in the twilight zone of sequence similarity. The database makes explicitly visible architectural similarities in the known part of the universe of protein folds and may be useful for understanding protein folding and for extracting structural modules for protein design. The data sets are available via Internet.