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Biomedical subjects

E Frey

Publications and source records attributed to E Frey.

At least 19 recordsLinked to original sources
PubMed2006

Microrheology probes length scale dependent rheology.

We exploit the power of microrheology to measure the viscoelasticity of entangled F-actin solutions at different length scales from 1 to 100 microm over a wide frequency range. We compare the behavior of single probe-particle motion to that of the correlated motion of two particles. By varying the average length of the filaments, we identify fluctuations that dissipate diffusively over the filament length. These provide an important relaxation mechanism of the elasticity between 0.1 and 30 rad/sec.

Actins↗
PubMed2005

Bimodality in the transverse fluctuations of a grafted semiflexible polymer and the diffusion-convection analogue: an effective-medium approach.

Recent Monte Carlo simulations of a grafted semiflexible polymer in 1+1 dimensions have revealed a pronounced bimodal structure in the probability distribution of the transverse (bending) fluctuations of the free end, when the total contour length is of the order of the persistence length [G. Lattanzi, Phys. Rev E 69, 021801 (2004)]. In this paper, we show that the emergence of bimodality is related to a similar behavior observed when a random walker is driven in the transverse direction by a certain type of shear flow. We adapt an effective-medium argument, which was first introduced in the context of the sheared random-walk problem [E. Ben-Naim, Phys. Rev. A 45, 7207 (1992)], in order to obtain a simple analytic approximation of the probability distribution of the free-end fluctuations. We show that this approximation captures the bimodality and most of the qualitative features of the free-end fluctuations. We also predict that relaxing the local inextensibility constraint of the wormlike chain could lead to the disappearance of bimodality.

Journal Article↗
PubMed2005

Melting of colloidal molecular crystals on triangular lattices.

The phase behavior of a two-dimensional colloidal system subject to a commensurate triangular potential is investigated. We consider the integer number of colloids in each potential minimum as rigid composite objects with effective discrete degrees of freedom. It is shown that there is a rich variety of phases including "herringbone" and "Japanese 6 in 1" phases. The ensuing phase diagram and phase transitions are analyzed analytically within variational mean-field theory and supplemented by Monte Carlo simulations. Consequences for experiments are discussed.

Journal Article↗
PubMed2005

Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system.

The aim of this study was to analyze cisplatin-induced ototoxicity in a recent study trial. Seventy-four patients who had received cisplatin for the treatment of osteosarcoma (median cumulative dose: 360 mg/m2) were investigated prospectively for ototoxicity in a multicenter trial. Hearing function was tested by audiometry. We evaluated the incidence and dependencies of hearing loss. After cessation of therapy, 51% of the patients showed a hearing loss of >20 dB in the frequency range of 4-8 kHz. Only in one patient a hearing loss was found at 2 kHz, and in none at 1 kHz. At a cumulative cisplatin dose of < or = 240 mg/m2, almost no ototoxicity was found. Incidence and magnitude of hearing loss increased significantly with a higher cumulative dose. Furthermore, hearing thresholds were significantly poorer in children <12 years. A further follow-up investigation showed only a marginal change in hearing function. We conclude that ototoxicity is moderate in our group of patients and probably irreversible.

Adolescent↗
PubMed2004

Totally asymmetric simple exclusion process with Langmuir kinetics.

We discuss a class of driven lattice gas obtained by coupling the one-dimensional totally asymmetric simple exclusion process to Langmuir kinetics. In the limit where these dynamics are competing, the resulting nonconserved flow of particles on the lattice leads to stationary regimes for large but finite systems. We observe unexpected properties such as localized boundaries (domain walls) that separate coexisting regions of low and high density of particles (phase coexistence). A rich phase diagram, with high and low density phases, two and three phase coexistence regions, and a boundary independent "Meissner" phase is found. We rationalize the average density and current profiles obtained from simulations within a mean-field approach in the continuum limit. The ensuing analytic solution is expressed in terms of Lambert W functions. It allows one to fully describe the phase diagram and extract unusual mean-field exponents that characterize critical properties of the domain wall. Based on the same approach, we provide an explanation of the localization phenomenon. Finally, we elucidate phenomena that go beyond mean-field such as the scaling properties of the domain wall.

Journal Article↗
PubMed2004

Transverse fluctuations of grafted polymers.

We study the statistical mechanics of grafted polymers of arbitrary stiffness in a two-dimensional embedding space with Monte Carlo simulations. The probability distribution function of the free end is found to be highly anisotropic and non-Gaussian for typical semiflexible polymers. The reduced distribution in the transverse direction, a Gaussian in the stiff and flexible limits, shows a double-peak structure at intermediate stiffnesses. We also explore the response to a transverse force applied at the polymer free end. We identify F-Actin as an ideal benchmark for the effects discussed.

Journal Article↗
PubMed2004

Validation of the German version of the Pediatric Quality of Life Inventory (PedsQL) in childhood cancer patients off treatment and children with epilepsy.

The Pediatric Quality of Life Inventory (PedsQL) is a relatively new instrument developed in the US to assess health-related quality of life (HRQL) in healthy and ill children and adolescents. It is quick and easy to use, suitable for assessment by children and parents and based on a modular approach with a generic measure addressing all general domains of HRQL and disease-specific modules. We report here the results of translating the original US generic core instrument and the cancer module into German and testing the German PedsQL in samples of paediatric patients who have been treated for cancer or epilepsy. Like in studies with the original instrument, score distributions tended to be skewed toward higher HRQL, but a full response range was demonstrated for each item. The German PedsQL is reliable in terms of internal consistency with the majority of scales exceeding a Cronbach's alpha of 0.70. Clinical validity was confirmed by differences between the cancer and epilepsy groups in the expected direction and by the ability of the PedsQL to discriminate between subjects with different degrees of medical and psychosocial sequelae. Comparing our findings to US results, the German PedsQL seems to be equivalent to the original version. Future methodologic research should evaluate construct validity, sensitivity and responsiveness, and test the usefulness of the instrument in other clinical populations and healthy children.

Adolescent↗
PubMed2003

Depinning of semiflexible polymers.

We present a theoretical analysis of a simple model of the depinning of an anchored semiflexible polymer from a fixed planar substrate in 1+1 dimensions. We consider a polymer with a discrete sequence of pinning sites along its contour. Using the scaling properties of the conformational distribution function in the stiff limit and applying the necklace model of phase transitions in quasi-one-dimensional systems, we obtain a melting criterion in terms of the persistence length, the spacing between pinning sites, a microscopic effective length that characterizes a bond, and the bond energy. The limitations of this and other similar approaches are discussed. We also consider the general problem of thermal depinning in 1+d dimensions. In the case of force-induced unbinding, it is shown that the bending rigidity favors the unbinding through a "lever-arm effect."

Journal Article↗
PubMed2003

Phase coexistence in driven one-dimensional transport.

We study a one-dimensional totally asymmetric exclusion process with random particle attachments and detachments in the bulk. The resulting dynamics leads to unexpected stationary regimes for large but finite systems. Such regimes are characterized by a phase coexistence of low and high density regions separated by domain walls. We use a mean-field approach to interpret the numerical results obtained by Monte Carlo simulations, and we predict the phase diagram of this nonconserved dynamics in the thermodynamic limit.

Journal Article↗
PubMed2001

Dynamics and cooperativity of microtubule decoration by the motor protein kinesin.

We describe a theoretical and experimental analysis of the interaction between microtubules and dimeric motor proteins (kinesin, NCD), with special emphasis on the stoichiometry of the interaction, cooperative effects, and their consequences for the interpretation of biochemical and image reconstruction results. Monomeric motors can bind equivalently to microtubules without interference, at a stoichiometry of one motor head per tubulin subunit (alphabeta-heterodimer). By contrast, dimeric motors can interact with stoichiometries ranging between one and two heads per tubulin subunit, depending on binding constants of the first head and the subsequent binding of the second head, and the concentration of dimers in solution. Further, we show that an attractive interaction between the bound motor molecules can explain the higher periodicities observed in decorated microtubules (e.g. 16 nm periodicity), and the non-uniform decoration of a population of microtubules and give an estimate of the strength of this interaction.

Allosteric Site↗
PubMed2001

Novel phases and reentrant melting of two-dimensional colloidal crystals.

We investigate two-dimensional (2D) melting in the presence of a one-dimensional (1D) periodic potential as, for example, realized in recent experiments on 2D colloids subjected to two interfering laser beams. The topology of the phase diagram is found to depend primarily on two factors: the relative orientation of the 2D crystal and the periodic potential troughs, which selects a set of Bragg planes running parallel to the troughs, and the commensurability ratio p=a(')/d of the spacing a(') between these Bragg planes to the period d of the periodic potential. The complexity of the phase diagram increases with the magnitude of the commensurabilty ratio p. Rich phase diagrams, with "modulated liquid," "floating," and "locked floating" solid and smectic phases are found. Phase transitions between these phases fall into two broad universality classes, roughening and melting, driven by the proliferation of discommensuration walls and dislocations, respectively. We discuss correlation functions and the static structure factor in these phases, and make detailed predictions about the universal features close to the phase boundaries. We predict that for charged systems with highly screened short-range interactions, these melting transitions are generically reentrant as a function of the strength of the periodic potential, a prediction that is in accord with recent 2D colloid experiments. Implications of our results for future experiments are also discussed.

Journal Article↗
PubMed2000

German cross-cultural adaptation of the Health Utilities Index and its application to a sample of childhood cancer survivors.

UNLABELLED: Steady progress in developing effective treatments for childhood cancer and other severe pediatric diseases has established the need to consider the nature and frequency of late physical and psychological effects. The Health Utilities Index Mark 2 and Mark 3 (HUI2/3) systems were developed by Feeny, Furlong, Torrance et al. in Canada. These systems are generic multi-attribute measures of a person's health status and health-related quality of life. The first German version of the Canadian HUI2/3 questionnaire was created in our clinic, following recommended guidelines for cross-cultural adaptation of health-related quality of life measures. The usefulness of the resultant version was investigated using a sample of 142 patients who presented to our oncological outpatients' department for a routine health care visit after completion of treatment. The 15 items of the HUI2/3-questionnaire were answered independently by three groups of assessors--nurses, physicians, and parents or patients. Two additional questions covered ratings of the severity of treatment effects and the specification of these effects. The questionnaire was both easy to use and acceptable to the assessors. Percentage agreement between observers about levels for individual attributes ranged from 56% to 100%, with the lowest agreement on the subjective attributes of emotion, pain and cognition. These results are in accordance with previous studies using the original instrument. HUI2 global utility scores were significantly related to ratings of treatment sequelae, giving support to the discriminant validity of the measure. CONCLUSION: The German version of HUI2/3 is a useful instrument with generally high inter-observer agreement and good suitability for outcome measurement in childhood cancer patients. Further research is needed to assess the usefulness of the instrument in other clinical populations and its sensitivity in longitudinal studies.

Child↗
PubMed2000

Human response to Escherichia coli O157:H7 infection: antibodies to secreted virulence factors.

Vaccination has been proposed for the prevention of disease due to enterohemorrhagic Escherichia coli (EHEC), but the immune response following human infection, including the choice of potential antigens, has not been well characterized. To study this, sera were obtained from five pediatric patients with acute diarrhea caused by E. coli O157:H7 0, 8, and 60 days after hospitalization. These sera were used to examine the immune response to four different EHEC virulence factors: Tir (translocated intimin receptor, which is inserted into the host cell membrane), intimin (bacterial outer membrane protein which binds to Tir), EspA (secreted protein which forms filamentous structures on EHEC surface), and EspB (inserted into the host membrane and cytoplasm). The response to O157:H7 lipopolysaccharide was also examined. Sera were assayed against purified recombinant proteins using immunoblot analysis and by enzyme-linked immunosorbent assay to determine the sera's titers to each of the antigens in all patients. We found that there was little reaction to EspA, EspB, and intimin in the acute-phase sera, although there was some reactivity to Tir. By day 8, titers of antibody to all four virulence factors were present in all patients, with a very strong response against Tir (up to a titer of 1:256,000), especially in hemolytic-uremic syndrome patients, and lesser strong responses to the other three antigens. The titer to the antigens 60 days after hospitalization was decreased but was still highest for Tir. These results suggest that there is a strong immune response to Tir, and to a lesser extent to the other three virulence factors, following EHEC disease, indicating that these bacterial molecules are potential vaccine candidates for preventing EHEC disease. They also suggest that bacterial virulence factors that are inserted into host cells during infection by type III secretion systems (Tir or EspB) are still recognized by the host immune response.

Adhesins, Bacterial↗
PubMed2000

[From program to metaphor--managing the needs of children in a separation or divorce process involving their parents].

In German-speaking regions there are several independent intervention programs, derived from concepts originating in the USA, which are designed to assist children whose parents are separated or divorced. Two of these programs will be presented here. Consistent with the thematic implication that divorce entails trauma and stress, the childrens' need of advice and help is placed at the conceptual center of the intervention. This results in a behavioral-cognitive training program, which should enable children to overcome the stress of their situation. In contrast to these two programs, an understanding of divorce may be achieved, through phenomenological analysis, which gives due consideration to the various aspects and meanings of the divorce process. The concept of intervention derived from this approach is to assist children in further developing their own search for solutions, focused on the parents-child-relation. The primary emphasis of this approach is not the childrens' difficulty in dealing with their parents' separation and divorce, but rather their own attempt to deal with the problem, as is visible in the metaphor of their spontaneous descriptions and images of experiences and events. The central concept of the proposed course is the further development of this creative process in the form of a dynamic-communicative group happening. Furthermore it is shown how children can be assisted in a practical way, and encouraged to create their individual and personally adequate solution to the experience of divorce.

Adaptation, Psychological↗
PubMed1999

[Multimodal therapy concepts in esophageal carcinoma: importance of radio- and chemotherapy].

Five-year survival of surgically treated patients with operable oesophageal carcinoma does not exceed 20%. The results with curative radiotherapy are even worse, with < or = 10% alive after 5 years. New treatment strategies are needed. Pre- or postoperative radiotherapy and perioperative chemotherapy alone do not improve survival. A simultaneous radiochemotherapy with cisplatin is significantly more effective than radiotherapy alone. A subgroup of patients with pathological complete remission after preoperative treatment (radio- and/or chemotherapy) survives significantly longer. It seems likely that survival in oesophageal cancer is improved by multimodal therapy encompassing radiotherapy, chemotherapy and surgery. Further randomised trials are needed, possibly in combination with other potentially active drugs.

Antineoplastic Agents↗
PubMed1998

Production and certification of an enzyme reference material for creatine kinase isoenzyme 2 (CRM 608).

We describe the preparation of a lyophilized material containing purified human creatine kinase 2 (CK-MB), and the certification of its catalytic concentration. The material can be used to verify the comparability of results from different laboratories, for intra-laboratory quality control, or for calibration of the creatine kinase 2 catalytic concentration measurements. The enzyme was purified from human heart by ethanol precipitation and chromatography successively on DEAE-Sephacel and Blue-Sepharose. The purified enzyme had a specific activity of 998.4 U/mg and was > 99% pure on polyacrylamide gel electrophoresis. The material was examined for several possible contaminating enzymes, which were found to be absent. The purified creatine kinase 2 had two subunits (B and M) with molecular masses of 43,650 and 41,700 g/mol, respectively, and an isoelectric point at pH 5.8. The material was prepared by diluting the purified creatine kinase 2 in a matrix containing 25 mmol/L PIPES buffer, pH 7.2, 2 mmol/L ADP, 5 mmol/L 2-mercaptoethanol, 154 mmol/L sodium chloride and 50 g/L human serum albumin, dispensing it into vials and freeze-drying. The batch was shown to be homogeneous. The loss of enzyme activity on storage at -20 degrees C is predicted to be less than 0.18% per annum on the basis of accelerated degradation studies. The catalytic concentration of creatine kinase in samples of the reconstituted material is certified to be 67.2+/-1.8 U/L (1.12+/-0.03 microkat/L) when measured, at 30 degrees C, by the Recommended Method of the International Federation of Clinical Chemistry.

Catalysis↗