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S Keller

Publications and source records attributed to S Keller.

At least 19 recordsLinked to original sources
PubMed2006

Intramolecular dynamics of linear macromolecules by fluorescence correlation spectroscopy.

A theoretical description of the dynamics of DNA molecules and actin filaments in solution as measured experimentally by fluorescence correlation spectroscopy is provided and compared to recent experimental results. Particular attention is paid to the contribution of the intramolecular dynamics to the fluorescence correlation function. Using a semiflexible chain model, a theoretical expression is presented for the fluorescence correlation spectroscopy correlation function. The dependence of this function on various model parameters, such as chain length, persistence length, and fluorescence label density, is discussed. Our investigations show that the intramolecular dynamics provides a significant contribution or even dominates the correlation function as soon as the longest intramolecular relaxation time significantly exceeds the shortest experimentally accessible time. Correspondingly, the shape of the correlation function changes considerably. Approximate analytical expressions are provided, which are in qualitative agreement with the exact theoretical solutions as well as experimental results, for both DNA and actin filaments. Our approach is in agreement with the predictions of the Zimm model, in the limit of very flexible polymers, as well as the predictions of semiflexible polymer models with respect to the intramolecular dynamics in solution.

Actin Cytoskeleton↗
PubMed2006

Hypoxic preconditioning and erythropoietin protect retinal neurons from degeneration.

Reduced tissue oxygenation stabilizes the alpha-subunit of the transcription factor hypoxia-inducible factor-1 (HIF-1). This leads to the induction of a number of hypoxia responsive genes. One of the best known HIF-1 targets is erythropoietin that exerts neuroprotective effects on ischemia-related injury in the brain. Thus, pre-exposure to low environmental oxygen concentrations might be exploited as a preconditioning procedure to protect tissues against a variety of harmful conditions. We present recent work on neuroprotection of retinal photoreceptors induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.

Animals↗
PubMed2006

Explaining socioeconomic status effects in laryngeal cancer.

INTRODUCTION: People with lower socioeconomic status (SES) experience shorter survival times after a cancer diagnosis for many disease sites. We determined whether area-level SES was associated with the outcomes: cause-specific survival and local-regional failure in laryngeal cancer in Ontario, Canada. When we found an association we sought explanations that might be related to access to care including age, sex, rural residence, tumor stage, lymph node status, use of diagnostic imaging, treatment type, percentage of prescribed radiotherapy delivered, number of radiotherapy interruption days, treatment waiting time, and treating cancer center. MATERIALS AND METHODS: The study population consisted of 661 glottic and 495 supraglottic stage-stratified randomly-sampled patients identified using the Ontario Cancer Registry. Area-level SES quintiles were assigned using adjusted median household income from the Canadian Census. Other data were collected from patient charts. Explanations for SES effects were determined by measuring whether the effect moved toward the null value by at least 10% when an access indicator was added to a the model. RESULTS: Socioeconomic status was not related to either outcome for those with supraglottic cancer, but an association was present in glottic cancer. With the highest socioeconomic status quintile as the referent group, the relative risks for patients in the lowest socioeconomic quintile were 2.75 (95% CI 1.48, 5.12) for cause-specific survival and 1.90 (95% CI 1.24, 2.93) for local-regional failure. Disease stage as measured by T-category explained between 3% and 23% of these socioeconomic effects. None of the other access indicators met our 10% change criterion. CONCLUSION: We question why people in lower socioeconomic quintiles were not diagnosed earlier in the disease progression. Having ruled out several variables that may be related to access to care, additional biologic and social variables should be examined to further understand socioeconomic status effects.

Adult↗
PubMed2005

Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action.

Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messengers from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d-chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called INS2). Here we show that chemically synthesized INS2 has biological activity that significantly enhances insulin reduction of hyperglycemia in streptozotocin diabetic rats. We used computer modeling to dock INS2 onto the known three-dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and FlexX/CScore energy minimization predicted a unique favorable site on PP2C for INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is predicted to involve formation of multiple H-bonds, including one with residue Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p-nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt the catalytic site. We propose that INS2 allosterically activates PP2C, fulfilling the role of a putative mediator mimetic of insulin signaling to promote protein dephosphorylation and metabolic responses.

Amino Acid Substitution↗
PubMed2005

Outcomes of a 2-year investigation on enhanced biological nutrients removal and trace organics elimination in membrane bioreactor (MBR).

Two configurations of membrane bioreactors were identified to achieve enhanced biological phosphorus and nitrogen removal, and assessed over more than two years with two parallel pilot plants of 2m3 each. Both configurations included an anaerobic zone ahead of the biological reactor, and differed by the position of the anoxic zone: standard pre-denitrification, or post-denitrification without dosing of carbon source. Both configurations achieved improved phosphorus removal. The goal of 50 microgP/L in the effluent could be consistently achieved with two types of municipal wastewater, the second site requiring a low dose of ferric salt ferric salt < 3 mgFe/L. The full potential of biological phosphorus removal could be demonstrated during phosphate spiking trials, where up to 1 mg of phosphorus was biologically eliminated for 10 mg BOD5 in the influent. The post-denitrification configuration enabled a very good elimination of nitrogen. Daily nitrate concentration as low as 1 mgN/L could be monitored in the effluent in some periods. The denitrification rates, greater than those expected for endogenous denitrification, could be accounted for by the use of the glycogene pool, internally stored by the denitrifying microorganisms in the anaerobic zone. Pharmaceuticals residues and steroids were regularly monitored on the two parallel MBR pilot plants during the length of the trials, and compared with the performance of the Berlin-Ruhleben WWTP. Although some compounds such as carbamazepine were persistent through all the systems, most of the compounds could be better removed by the MBR plants. The influence of temperature, sludge age and compound concentration could be shown, as well as the significance of biological mechanisms in the removal of trace organic compounds.

Anaerobiosis↗
PubMed2004

Flow profiling of a surface-acoustic-wave nanopump.

The flow profile in a capillary gap and the pumping efficiency of an acoustic micropump employing surface acoustic waves is investigated both experimentally and theoretically. Ultrasonic surface waves on a piezoelectric substrate strongly couple to a thin liquid layer and generate a quadrupolar streaming pattern within the fluid. We use fluorescence correlation spectroscopy and fluorescence microscopy as complementary tools to investigate the resulting flow profile. The velocity was found to depend on the applied power approximately linearly and to decrease with the inverse third power of the distance from the ultrasound generator on the chip. The found properties reveal acoustic streaming as a promising tool for the controlled agitation during microarray hybridization.

Acoustics↗
PubMed2004

Limits for the central production of Theta+ and Xi(--)pentaquarks in 920-GeV pA collisions.

We have searched for Theta+(1540) and Xi(--)(1862) pentaquark candidates in proton-induced reactions on C, Ti, and W targets at midrapidity and square root of s = 41.6 GeV. In 2 x 10(8) inelastic events we find no evidence for narrow (sigma approximately 5 MeV) signals in the Theta+ --> pK0(S) and Xi(--) --> Xi- pi- channels; our 95% C.L. upper limits (UL) for the inclusive production cross section times branching fraction B dsigma/dy/(y approximately 0) are (4-16) mub/N for a Theta+ mass between 1521 and 1555 MeV, and 2.5 mub/N for the Xi(--). The UL of the yield ratio of Theta+/Lambda(1520) < (3-12)% is significantly lower than model predictions. Our UL of B Xi(--)/Xi(1530)0 < 4% is at variance with the results that have provided the first evidence for the Xi(--).

Journal Article↗
PubMed2004

Self-diffusion of rodlike and spherical particles in a matrix of charged colloidal spheres: a comparison between fluorescence recovery after photobleaching and fluorescence correlation spectroscopy.

The fluorescence recovery after photobleaching (FRAP) method and the fluorescence correlation spectroscopy (FCS) have been applied on suspensions of highly charged colloidal spheres with a small content of rod-shaped tobacco mosaic virus (TMV) particles. Since these methods only determine the self-diffusion coefficient of the fluorescently labeled species, D(S) of the rods and the spheres could independently be measured. The ionic strength of the dispersion medium has been varied to measure self-diffusion of rods and spheres in dependence on the degree of order of the matrix spheres. In contrast to FRAP, which allows the determination of the long-time self-diffusion coefficient D(S) (L), FCS measures self-diffusion on a shorter time scale. Thus a comparison of the results that were obtained by FCS and FRAP, in combination with Brownian Dynamics simulations, gives insight into the time dependence of the self-diffusion coefficient of an interacting colloidal system. As the mean interparticle distance of the matrix is of the same order of magnitude as the length of a TMV rod, the rotational motion is influenced by the assembly of spheres around a TMV particle. Since FCS is sensitive both to translational and rotational motion, whereas FRAP, which probes the diffusion at much larger length scales, is only sensitive to the translational motion of TMV, the comparison of diffusion coefficients measured employing FRAP and FCS can give some insights in the rotational diffusion: the experimental data indicate a slowing down of the rotational motion of a TMV rod with increasing structural order of the matrix spheres.

Journal Article↗
PubMed2003

Dynamics of large semiflexible chains probed by fluorescence correlation spectroscopy.

Fluorescence correlation spectroscopy was used to probe the dynamics of lambda-phage DNA in aqueous solution labeled with the randomly intercalating dye TOTO. The linear macromolecules (i). carry more than one chromophore and (ii). are larger than the waist of the focal volume. The correlation function decays significantly faster than expected for a stiff globule of corresponding size but is in good agreement with the dynamic model of semiflexible chains including hydrodynamic interactions. As the chromophore density is lowered the correlation time decreases in accordance with this model.

Bacteriophage lambda↗
PubMed2003

[Analysis of direct costs in therapy of Parkinson disease].

The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.

Aged↗
PubMed2003

Entomophthora leyteensis Villacarlos & Keller sp. nov. (Entomophthorales: Zygomycetes) infecting Tetraleurodes acaciae (Quaintance) (Insecta, Hemiptera: Aleyrodidae), a recently introduced whitefly on Gliricidia sepium (Jaq.) Walp. (Fabaceae) in the Philippines.

Entomophthora leyteensis Villacarlos & Keller sp. nov., a species of Entomophthorales infecting the whitefly Tetraleurodes acaciae on Gliricidia sepium in the Philippines is described. Disease prevalence monitored weekly for 8 weeks indicated that the fungus could cause 8-31% infection within the whitefly population. Epizootics due to this fungus occurred in Inopacan, Leyte. Sampling live whitefly adults and dissecting them on glass slides for microscopic examination of fungal structures was found to give a better measure of prevalence than actual counts of infected insect cadavers. E. leyteensis is an important mortality factor for T. acaciae. Some speculations on the origin of the fungus are discussed here.

Animals↗
PubMed2003

Influence of radiographic contrast media on myocardial tissue oxygen tension: NaCl-controlled, randomised, comparative study of iohexol versus iopromide in an animal model.

It was tested whether a bolus injection of 10 ml radiographic contrast medium (iopromide vs. iohexol), compared to a 10 ml NaCl bolus and administered into the left anterior descending artery (LAD) of farm pigs, influenced the tissue pO2 in the territory of this artery. The radiographic contrast media and the NaCl bolus were given in randomised order. The mean pO2 LAD fell from initially 40.3+/-10.9 mmHg to a minimal value of 22.5+/-8.9 mmHg 241+/-44 sec after injecting the iopromide bolus, with this result representing a mean decrease of 44.2% (p=0.0003). The initial pO2 (baseline) was reached again after approximately 10 minutes. The mean pO2 LAD fell from the initial value of 34.5+/-14.6 mmHg to a minimal value of 29.4+/-13.9 mmHg 171.7+/-11.9 sec after injection of the iohexol bolus, with this result representing a mean decrease of 14.8% (p=0.0003). The baseline pO2 was reached again after approx. 5 minutes. The drop in the pO2 after iopromide administration was significantly larger than that after iohexol (p=0.0001), and also the time after which the baseline pO2 is reached again was considerably shorter for iohexol (p=0.001). The two radiographic contrast media did not influence the tissue pO2 in either the territory of the right coronary artery or in skeletal muscle. Injection of a NaCl bolus into the LAD influenced neither the tissue pO2 of the territory of the LAD nor that of the RCA or of the skeletal muscle. The tissue temperature, heart rate and the systolic and diastolic blood pressure were not affected during the three injections. Injection of radiographic contrast media into a coronary artery can lead to a distinct, local microcirculatory impairment in the myocardial territory supplied by this artery. In this case, the extent of the microcirculation impairment seems to depend not only on the viscosity of the contrast media but rather also on its chemotoxicity.

Animals↗
PubMed2002

Modulators of internal Ca2+ stores and the spontaneous electrical and contractile activity of the guinea-pig renal pelvis.

1. The role of internal Ca(2+) stores in the generation of the rhythmic electrical and contractile activity in the guinea-pig proximal renal pelvis was examined using intracellular microelectrode and muscle tension recording techniques. 2. Ryanodine (30 microM) transiently increased contraction amplitude, while caffeine (0.5 - 3 mM) reduced contraction amplitude and frequency. Contractility was also reduced by 2-aminoethoxy-diphenylborate (2-APB 60 microM), xestospongin C (1 microM), U73122 (5 microM) and neomycin (4 mM), blockers of IP(3)-dependent release from Ca(2+) stores. 3. 60 mM K(+) saline-evoked contractions were reduced by caffeine (1 mM), U73122 (5 microM) and neomycin (4 mM), but little affected by ryanodine or 2-APB (60 microM). 4. Spontaneous action potentials consisting of an initial spike followed by a long plateau were recorded (frequency 8.6+/-1.0 min(-1)) in small urothelium-denuded strips of proximal renal pelvis. 5. Action potential discharge was blocked in 75 and 35% of cells by 2-APB (60 microM) and caffeine (1 mM), respectively. In the remaining cells, only a truncation of the plateau phase was observed. 6. Cyclopiazonic acid (CPA 10 microM for 10 - 180 min), blocker of CaATPase, transiently increased contraction frequency and amplitude. Action potential durations were increased 3.6 fold. Contraction amplitude and frequency slowly declined during a prolonged (>60 min) CPA exposure. 7. We conclude that the action potential in caffeine-sensitive cells and the shoulder component of caffeine-insensitive action potential arise from the entry of Ca(2+) through Ca(2+) channels. The inhibitory actions of modulators of internal Ca(2+) release were partially explained by a blockade of Ca(2+) entry.

Animals↗
PubMed2002

Apomorphine sensitization: evoking conditions, context dependence, effect persistence and conditioned nature.

When repeatedly administered a dose of apomorphine (Apo), pigeons, much like rodents, show behavioural sensitization. In birds this sensitization expresses itself as an increasing pecking response to the drug and is found to be partially dependent on the environmental context in which Apo takes effect. In the first experiment we examined what effect different inter-Apo administration intervals have on the development of Apo sensitization and found that, with some smaller variations, intervals between 3 hours and 5 days all yielded comparable courses of sensitization. In the second experiment we examined how long pigeons had to be exposed to the same distinct cage to reveal a maximal context-dependent sensitization. Pigeons were therefore repeatedly injected with Apo and consistently placed in an experimental cage for different lengths of time (5 to 60 min; the overall drug effect lasted for about 1 h) before being returned to their standard home cages. Subsequent tests in the experimental cage and a standard cage showed that 20-min post-injection exposures were sufficient to yield a maximal response in the experimental cage. After training with 20- and 60-min exposures, the pigeons pecked about three times more in the experimental cage than in the standard cage. This confirmed the marked context dependency of the sensitization effect. In the third experiment, groups of pigeons were injected repeatedly with Apo and directly afterwards placed either consistently into the same experimental cage or into different experimental cages. The same-cage group evidenced a significantly much stronger sensitization than the different-cage group. A cage-habituation group served as a control for the possibility that the weaker sensitization of the different-cage group might be due to a cage novelty effect. This cage-habituation group was run under the same conditions as the different-cage group but with additional exposures to the crucial cage while injected with saline. This extra treatment did not augment the pecking response to Apo in that cage. In the fourth experiment we examined how long the sensitization to Apo lasts and found that, even after 2 years of drug abstinence, it only waned to 50% of the original asymptotic response. The overall results support the hypothesis that a very major part of the sensitization to Apo in pigeons is due to a conditioning to the environmental context and to the drug state itself.

Animals↗
PubMed2002

Willem Einthoven--inventor of electrocardiography.

Willem Einthoven, the inventor of the string galvanometer electrocardiograph, was born in the Dutch East Indies, studied medicine in Utrecht Holland, and became chairman of the Department of Physiology at the University of Leiden. In 1924 he was awarded the Nobel Price for physiology and medicine. Einthoven became interested in electrophysiology after Waller's demonstration of the human electrogram using Lippmann's capillary electrometer. Because of important limitations of this device, Einthoven decided to construct the string galvanometer to be used for physiological research and in clinical medicine. Einthoven's main achievements in electrophysiology were the description of the normal ECG, some physiological effects on the ECG, the three ECG leads and the triangle rule. In 1906 in cooperation with the university hospital, Einthoven demonstrated the clinical usefulness of the electrocardiograph.

Electrocardiography↗
PubMed2002

A history of atrial fibrillation.

Vulpian in France and Hoff and Ludwing in Germany first studied atrial fibrillation in experimental animals. In clinical medicine, de Senac and others, first observed irregular and fast pulse. Hering in 1903 described "pulsus irregularis perpetuus" as a distinct arrhythmia. Hering believed, that this was an extrasystolic rhythm disturbance, while Cushny and Edmunds suggested atrial fibrillation as its cause. Mackenzie was another British author who played an important role in the clarification of atrial fibrillation, particularly after Cushny convinced him, that the so-called nodal rhythm was atrial fibrillation. Einthoven reported the first ECG of atrial fibrillation without recognizing its true nature. Finally in 1909 and 1910 Lewis in London and, Rothberger and Winterberg in Vienna established atrial fibrillation as a clinical entity.

Atrial Fibrillation↗
PubMed2001

Adenovirus-activated PKA and p38/MAPK pathways boost microtubule-mediated nuclear targeting of virus.

Nuclear targeting of adenovirus is mediated by the microtubule-dependent, minus-end-directed motor complex dynein/dynactin, in competition with plus- end-directed motility. We demonstrate that adenovirus transiently activates two distinct signaling pathways to enhance nuclear targeting. The first pathway activates integrins and cAMP-dependent protein kinase A (PKA). The second pathway activates the p38/MAP kinase and the downstream MAPKAP kinase 2 (MK2), dependent on the p38/MAPK kinase MKK6, but independent of integrins and PKA. Motility measurements in PKA-inhibited, p38-inhibited or MK2-lacking (MK2(-/-)) cells indicate that PKA and p38 stimulated both the frequency and velocity of minus-end-directed viral motility without affecting the perinuclear localization of transferrin-containing endosomal vesicles. p38 also suppressed lateral viral motilities and MK2 boosted the frequency of minus-end-directed virus transport. Nuclear targeting of adenovirus was rescued in MK2(-/-) cells by overexpression of hsp27, an MK2 target that enhances actin metabolism. Our results demonstrate that complementary activities of PKA, p38 and MK2 tip the transport balance of adenovirus towards the nucleus and thus enhance infection.

Adenoviruses, Human↗