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PubMed1990

An examination of Mann's model of time-limited individual psychotherapy.

The present study attempted a sensitive test of the dynamic sequence proposed by Mann for time-limited individual psychotherapy (TLP). Session evaluation ratings were collected from both patient and therapist. Indices were constructed that reflected the consistency of patient ratings, the consistency of therapist ratings, and the congruence between patient and therapist ratings, in each third of TLP. Measures of symptoms and social functioning were employed to differentiate cases of "good" versus "poor" treatment outcome. Therapists' adherence to the TLP technique was assessed by categorizing all interventions in each session. Fourteen patients were treated according to the TLP model. Measures of therapist behaviour indicated that treatments had been conducted in general accordance with Mann's technical recommendations. Measures of consistency and congruence failed to support the proposed TLP dynamic sequence. Analyses of mean evaluation ratings indicated a trend towards more positive evaluations as therapy progressed; "good" outcome cases were significantly more likely to evidence this pattern. Results are discussed in terms of interplay between inductive hypothesis building and empirical verification in the development of theories of psychotherapy.

Adaptation, Psychological↗
PubMed2001

Quod erat demonstrandum? The mystery of experimental validation of apparently erroneous computational analyses of protein sequences.

BACKGROUND: Computational predictions are critical for directing the experimental study of protein functions. Therefore it is paradoxical when an apparently erroneous computational prediction seems to be supported by experiment. RESULTS: We analyzed six cases where application of novel or conventional computational methods for protein sequence and structure analysis led to non-trivial predictions that were subsequently supported by direct experiments. We show that, on all six occasions, the original prediction was unjustified, and in at least three cases, an alternative, well-supported computational prediction, incompatible with the original one, could be derived. The most unusual cases involved the identification of an archaeal cysteinyl-tRNA synthetase, a dihydropteroate synthase and a thymidylate synthase, for which experimental verifications of apparently erroneous computational predictions were reported. Using sequence-profile analysis, multiple alignment and secondary-structure prediction, we have identified the unique archaeal 'cysteinyl-tRNA synthetase' as a homolog of extracellular polygalactosaminidases, and the 'dihydropteroate synthase' as a member of the beta-lactamase-like superfamily of metal-dependent hydrolases. CONCLUSIONS: In each of the analyzed cases, the original computational predictions could be refuted and, in some instances, alternative strongly supported predictions were obtained. The nature of the experimental evidence that appears to support these predictions remains an open question. Some of these experiments might signify discovery of extremely unusual forms of the respective enzymes, whereas the results of others could be due to artifacts.

Acetyltransferases↗
PubMedDate not supplied

Ultrasound applicators with integrated catheter-cooling for interstitial hyperthermia: theory and preliminary experiments.

Theoretical and experimental methods were used to evaluate a design of ultrasound applicators for interstitial hyperthermia. The basic schema consists of a multielement array of tubular piezoceramic radiators (1.5-1.6 mm diameter), each 5-10 mm long with separate power control, designed to be inserted within a 13-14 gauge closed-end brachytherapy implant catheter. Channels for circulating temperature-regulated water are integrated within the applicator to provide control of the catheter/tissue interface temperature. A quantitative theoretical analysis was undertaken to determine heating performance as a function of applicator spacing, blood perfusion, catheter material, frequency and required acoustic power output. Prototype multielement applicators were constructed and characterized in terms of acoustic pressure-squared distributions and acoustic power output capabilities. This study demonstrated distinct advantages of these catheter-cooled multielement ultrasound applicators within an implant, including higher T90's achievable within highly perfused tissues, dynamic control of the longitudinal power deposition, and no interaction between adjacent applicators or elements or sensitivity to applicator alignment. Preliminary measurements of prototype devices have indicated that implementation of these interstitial ultrasound applicators with integrated catheter-cooling is practicable, yet further development and in vivo verification of performance is warranted.

Acoustics↗
PubMed2001

Separation selectivity patterns in the capillary electrophoretic separation of anionic enantiomers by octakis-6-sulfato-gamma-cyclodextrin.

The capillary electrophoretic separation of anionic enantiomers with multiply-charged, single-isomer, anionic resolving agents was reexamined with the help of the charged resolving agent migration model. Three general model parameters were identified that influence the shape of the separation selectivity and enantiomer mobility difference curves: parameter b, the binding selectivity (K(RCD)/K(SCD)), parameter s, the size selectivity (micro0RCD/micro0SCD), and parameter a, the complexation-induced alteration of the analyte's mobility (micro0SCD/micro0). Function analysis of the model indicates that there are six unique separation selectivity vs. resolving agent concentration patterns: in two of the patterns, separation selectivity asymptotically increases to the limiting value set by parameter b; in two other patterns, separation selectivity passes a local maximum and asymptotically decreases to the limiting value set by parameter b; and in the last two patterns, separation selectivity passes a local maximum, decreases to unity, then, after reversal of the intrinsic migration order, asymptotically increases to the limiting value set by parameter b. Though the patterns with asymptotically increasing selectivities were observed in earlier work, this paper reports the first experimental verification of the existence of the local selectivity maximum during the capillary electrophoretic separation of the enantiomers of several weak acids in high pH background electrolytes with octakis-6-sulfato-gamma-cyclodextrin as the resolving agent.

Cyclodextrins↗
PubMed2006

Environmental induction of CYP1A-, CYP2M1- and CYP2K1-like proteins in tropical fish species by produced formation water on the northwest shelf of Australia.

Normal operation of oil well platforms results in the discharge of "produced formation water" (PFW). The expression of CYP1A, CYP2M1- and 2K1-like proteins was examined for use as possible biomarkers of PFW exposure. A pilot study at the Harriet A production platform, on the Northwest Shelf of Australia, had indicated that PFW contamination possibly contributes to induction of CYP1A- and 2K1/2M1-like proteins in Gold-Spotted Trevally (Carangoides fulvoguttatus). In a subsequent caged fish study in the same location, Stripey seaperch (Lutjanus carponotatus) were caught at a clean site, then distributed to three caging sites: A (near-field), B (far-field) and C (a non-impacted reference site). Fish were sampled at time T = 0, 3 and 10 days. Significant increases of CYP1A, one CYP2K1- and two CYP2M1-like proteins were noted at Site A at T = 10. For another CYP2K1-like protein, a significant increase was observed at Site A only at T = 3. Prevailing winds changed between days 6 and 8 of sampling, moving the surface water plume directly west, possibly impacting in situ PFW exposure. The results indicate that tropical fish CYP1A protein is sensitive to PFW exposure. Importantly, statistically significant environmental induction of both CYP2M1- and CYP2K1-like proteins in tropical fish due to PFW exposure had not previously been described and CYP2 family induction may represent possible new biomarkers (other than CYP1A) of PFW exposure. In addition, the novel fraction-specific response of CYP2K-like proteins requires further verification but offers promise for improved monitoring of sub-lethal responses in marine organisms. (Supported by Australian Institute of Marine Science, Apache Energy Ltd. and the Environmental Toxicology Research Program at The University of Mississippi).

Animals↗
PubMed2002

Assembly of alpha-helical peptide coatings on hydrophobic surfaces.

The adsorption or covalent attachment of biological macromolecules onto polymer materials to improve their biocompatibility has been pursued using a variety of approaches, but key to understanding their efficacy is the verification of the structure and dynamics of the immobilized biomolecules. Here we present data on peptides designed to adsorb from aqueous solutions onto highly porous hydrophobic surfaces with specific helical secondary structures. Small linear peptides composed of alternating leucine and lysine residues were synthesized, and their adsorption onto porous polystyrene surfaces was studied using a combination of solid-state NMR techniques. Using conventional solid-state NMR experiments and newly developed double-quantum techniques, their helical structure was verified. Large-amplitude dynamics on the NMR time scale were not observed, suggesting irreversible adsorption of the peptides. Their association, adsorption, and structure were examined as a function of helix length and sequence periodicity, and it was found that, at higher solution concentrations, peptides as short as seven amino acids adsorb with defined secondary structures. Two-dimensional double-quantum experiments using (13)C-enriched peptide sequences allow high-resolution determination of secondary structure in heterogeneous environments where the peptides are a minor component of the material. These results shed light on how polymeric surfaces may be surface-modified by structured peptides and demonstrate the level of molecular structural and dynamic information solid-state NMR can provide.

Amino Acid Sequence↗
PubMed2006

Electronic portal imaging based on cerenkov radiation: a new approach and its feasibility.

Most electronic portal imaging devices (EPIDs) developed so far use a Cu plate/phosphor screen to absorb x rays and convert their energies into light, and the light image is then read out. The main problem with this approach is that the Cu plate/phosphor screen must be thin (approximately 2 mm thick) in order to obtain a high spatial resolution, resulting in a low x-ray absorption or low quantum efficiency for megavoltage x rays (typically 2-4%). In addition, the phosphor screen contains high atomic number (high-Z) materials, resulting in an over-response of the detector to low-energy x rays in dosimetric verification. In this paper, we propose a new approach that uses Cerenkov radiation to convert x-ray energy absorbed by the detector into light for portal imaging applications. With our approach, a thick (approximately 10-30 cm) energy conversion layer made of a low-Z dielectric medium, such as a large-area, thick fiber-optic taper consisting of a matrix of optical fibers aligned with the incident x rays, is used to replace the thin Cu plate/phosphor screen. The feasibility of this approach has been investigated using a single optical fiber embedded in a solid material. The spatial resolution expressed by the modulation transfer function (MTF) and the sensitivity of the detector at low doses (approximately one Linac pulse) have been measured. It is predicted that, using this approach, a detective quantum efficiency of an order of magnitude higher at zero frequency can be obtained while maintaining a reasonable MTF, as compared to current EPIDs.

Equipment Design↗
PubMed1998

Linear accelerator output variations and their consequences for megavoltage imaging.

An experimental study of radiation output intensity fluctuations of a Philips SL25 linear accelerator is presented. Measurements are obtained using an electronic portal imaging device, and the consequences of the measured fluctuations for various different applications of megavoltage imaging including portal imaging, transit dosimetry and megavoltage computed tomography (MVCT) are discussed with examples. Fluctuations in output of +/- 0.7% (1 SD) are seen on every radiation pulse after photon noise and uncertainties caused by the detection system have been accounted for. Large fluctuations are also seen during the initial beam stabilization period (15%), during normal accelerator operation after the beam has been on for more than 1 min (4.5%) and during are therapy as a repeatable function of gantry angle (9%). Such output intensity fluctuations are shown to produce image artifacts in portal imaging devices with scanned detector readout and can also produce systematic errors in detector calibration that would lead to uncertainty in transit dose calculations. The propagation of these intensity fluctuations through MVCT image reconstruction is shown to produce ring artifacts in the reconstructed image. Sample portal and MVCT images are presented. All observed fluctuations in accelerator output are well within the manufacturer's specifications and do not affect the total dose delivered during normal treatment. Finally, megavoltage imaging is shown to be a powerful tool for accelerator quality assurance and treatment verification.

Calibration↗
PubMed1993

Simulation and optimisation of a self-regulating insulin delivery system.

The delivery of insulin is an integral part of the treatment of diabetes. It has been shown that an implantable polymeric system which releases insulin in response to blood glucose levels is feasible. This work aims to guide further experimental development of this system by constructing a mathematical model of the polymer matrix and analysing its functional characteristics by computer simulations. The system is an implantable polymer containing tri-lysyl insulin and the enzyme glucose-oxidase, and the feedback mechanism is based on the enzymatic reaction between glucose and glucose-oxidase. Acid produced from this reaction reduces the pH in the microenvironment of the polymer, which causes an increase in insulin solubility and release rate. The model was developed on the basis of the physical and chemical properties of the system, which were chosen in the light of direct observations with scanning electron microscopy combined with experimental measurements and reported values, and was validated by comparison with experimental results and by verification of some of its assumptions. Optimisation was undertaken by simulating the effect of different parameters of the system on its performance. Enzyme concentration, pore length, particle size and insulin loading were found to have surprisingly little effect. However, performance was significantly improved by using a hypothetical insulin molecule with a different solubility characteristic. The study can therefore provide a rational basis for the experimental development of a polymer-based artificial pancreas.

Algorithms↗
PubMed2001

Changes in gene expression following induction of ischemic tolerance in rat brain: detection and verification.

Tolerance against ischemic insults can be elicited in the CA1 region of rat hippocampus by inducing a short ischemic period 2-3 days prior to the ischemic insult. To detect genes whose expression changes following induction of ischemic tolerance (IT), we applied a differential display technique called restriction fragment differential display-PCR (RFDD-PCR). RFDD-PCR displays the coding region of mRNA and allows detection of differentially expressed mRNA. Double-stranded cDNA generated using a T25V primer is digested by the endonuclease TaqI, and adapters are ligated onto the cDNA fragments. When amplifying the adapter-containing cDNA fragments under high-stringency conditions, reproducible PCR profiles are obtained. By comparing these profiles from naïve and ischemia-tolerant rat brains statistically, significant expression changes of 20 fragments were identified. To verify the observed changes, quantitative PCR and in situ hybridization were performed for three fragments representing proteins with quite different functions (GluR2-flop, SC1, and p68 RNA helicase). Quantitative PCR displayed the same degree of regulation as RFDD-PCR, but in situ hybridization did not display any regulation. As the applied PCR-based techniques detect only polyadenylated mRNA, whereas in situ hybridization detects both nonadenylated and adenylated mRNA, changes in the polyadenylation state of the mRNA, rather than inconsistent changes in the total amount of mRNA, probably explain this discrepancy. Thus, our results show that the expression of genes hitherto not related to IT changes with the induction of IT and that the degree of regulation displayed by RFDD-PCR can be verified by quantitative PCR.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1995

Holter functions of the implantable cardioverter defibrillator: what is still missing?

The technology of the implantable cardioverter defibrillator (ICD) offers the opportunity to overcome the present limits of the invasive and noninvasive approaches of clinical electrophysiology. The invasive approach enables us to reproduce severe arrhythmias if they are inducible, but does not give information concerning the way they spontaneously arise. The noninvasive approach (Holter) gives this information, but it usually concerns only trivial arrhythmias with different therapeutic targets. One hopes in the future, by means of an important extension to ICD technology, which is not technically possible for the time being, to have access to pertinent information and to a better understanding of the circumstances leading to severe spontaneous arrhythmias, potentially lethal. For the moment, we only have the diagnostic certainty leading to the therapeutic intervention. It is based on an ECG and on the sequence of cardiac cycles preceding the rhythmic controlled accident. These data allow verification of but not explanation of the events. To have a chance to be understood and explained, these "events" must be replaced in the context of the "nonevents." Ideally, one should have all the gross information concerning the last 24 hours and subsequently analyze them. It is already a big step, thanks to the defibrillators the right to therapeutic error has been gained, a unique and fatal accident has been transformed into a repeatable event, and therefore, access is gained to the evolution of the responsible disease.

Defibrillators, Implantable↗
PubMed1993

Verification of a model of a F(ab) complex with phenylarsonate by oligonucleotide-directed mutagenesis.

A model of the combining site of a mouse antibody specific for p-azophenylarsonate was tested by oligonucleotide-directed mutagenesis of the proposed hapten-contacting residues, Arg96 in the L chain, and Asn35, Trp47, Tyr50, Ser95, and Tyr100b in the H chain. The affinity and relative affinity for p-azophenylarsonate-N-acetyl-L-tyrosine of mutant antibodies expressed in transfectomas were determined by fluorescence quenching and by inhibition ELISA, respectively. The results show that alteration of the proposed contacting residues has drastic effects on hapten binding, and that the hydroxyl groups of Tyr50 and Tyr100b appear to orient the phenyl rings for optimal aromatic-aromatic interactions with the phenyl ring of the hapten. They further indicate a tight packing of the contacting residues around the hapten, which cannot accommodate changes in the positions of the functional groups of Asn35 and Ser95.

Antibody Affinity↗
PubMed2006

Experimental and theoretical study of the electronic spectrum of the methylene amidogen radical (H2CN): verification of the 2A1 <-- 2B2 assignment.

A collaborative experimental and theoretical study of the electronic spectrum and excited-state photochemistry of H(2)CN has been carried out. The absorption spectrum, in the range of 287-278 nm, was measured through cavity ring-down spectroscopy. The radical was prepared by 193 nm photolysis of monomeric formaldoxime vapor. Two diffuse features were observed in the 34800-35800 cm(-1) spectral range, along with the A-X (1,0) band of the OH cofragment. The broad features were assigned through high-level ab initio calculations as vibronic transitions to the ground and 2b(1) (umbrella mode) levels of the second excited B (2)A(1) state from the ground X (2)B(2) state of H(2)CN. Rotational constants for the lower and upper levels of these transitions were computed from the expectation values of the moments of inertia tensor, using the appropriate vibrational wave functions. Experimental and simulated rotational profiles of these bands agree extremely well with each other for an assumed type-B electric dipole-allowed (2)A(1) <-- (2)B(2) transition appropriate to this transition. The former assignment to the dipole-forbidden (2)B(1) <-- (2)B(2) transition can be ruled out by these results. A theoretical investigation of the dissociation pathways for electronically excited H(2)CN is also presented. The upper states of the observed bands cannot dissociate directly but rather decay through internal conversion and subsequent dissociation to H + HCN fragments; higher b(1) levels are above the excited-state dissociation limit.

Journal Article↗
PubMed2005

Thallium-201 versus Tc99m-glucoheptonate SPECT for evaluation of recurrent brain tumours: a within-subject comparison with pathological correlation.

BACKGROUND: Thallium-201 (Tl-201) is the most commonly used tracer for functional imaging of recurrent brain tumours. However, the physical properties of Tl-201 are not particularly suitable for this application, thus, a technetium-99 (Tc99m) labelled alternative with more favourable physical properties has been sought. The aim of this study was to compare the ability of Tl-201 and Tc99m-glucoheptonate single photon emission computed tomography (SPECT) to detect viable recurrent tumour and differentiate post-radiation gliosis. METHOD: Brain SPECT with Tl-201 and Tc99m-glucoheptonate was performed in 20 patients with malignant brain tumour in whom recurrent disease was suspected. Tracer uptake in the mass was defined as high, moderate or low and was correlated with histological verification of the lesion in all cases. RESULTS: Recurrent tumour was demonstrated in 17 patients by both Tl-201 and Tc99m-glucoheptonate SPECT and confirmed by surgical resection in all 17 patients. Three patients had no tracer uptake on either Tl-210 or Tc99m-glucoheptonate SPECT and surgical resection revealed only fibrotic tissue with areas of necrosis. Tc99m-glucoheptonate images were found to correlate more closely with the surgical findings with regard to the location of tumour margin, extent of tumour invasion and intratumoural necrosis. CONCLUSION: Tc99m-glucoheptonate brain SPECT is an accurate agent for SPECT imaging of recurrent brain tumours and may provide more information about the location of the tumour margin and its extent and intratumoural necrosis than Tl-201. Tc99m-glucoheptonate may be a viable replacement for Tl-201.

Adolescent↗
PubMed1993

Spatial and temporal characteristics of rapid cursor-positioning movements with electromechanical mice in human-computer interaction.

This research examines how people make movements with pointing devices during human-computer interaction. It specifically concerns the perceptual-motor processes that mediate the speed and accuracy of cursor positioning with electromechanical mice. In three experiments we investigated the spatial and temporal characteristics of positioning movements made with a mouse, analyzing subjects' speed and accuracy as a function of the types of targets that the movements had to reach. Experiment 1 required rapid and accurate horizontal movements to targets that were vertical ribbons located at various distances from the mouse's starting location. The targets for Experiments 2 and 3, respectively, were vertical lines having various heights and rectangular boxes having various heights and widths. Constraints on movement distance along the primary (that is, horizontal) line of motion had the greatest effects on total positioning times. However, constraints on movement distance along a secondary (vertical) line of motion also affected total positioning times significantly. These effects may be localized in different phases of movements (e.g., movement execution and verification). The duration of movement execution (i.e., physical motion) depends primarily on the target distance, whereas the duration of movement verification (i.e., check for endpoint accuracy) depends primarily on target height and width. A useful account of movement execution is provided by stochastic optimized-submovement models, which have significant implications for designing mice and menu-driven displays.

Adult↗
PubMed2005

Purification of recombinant tau protein and preparation of Alzheimer-paired helical filaments in vitro.

The tau protein is a neuronal microtubule-associated protein. Apart of its physiological function-the binding to and stabilization of microtubules-tau is found in Alzheimer's disease brain as insoluble fibers, the so-called "paired helical filaments" (PHFs). Investigating the fundamentals of tau polymerization is indispensable for identifying inhibitory conditions or compounds preventing PHF formation, which may slow down or even stop the degeneration of neurons in Alzheimer's disease. In this chapter, we describe the methods necessary for studying the characteristics of tau polymerization to PHFs. These include: a purification protocol for recombinantly expressed tau; a general method for the polyanion induced polymerization of tau to PHFs; the quantitation of PHFs by a fluorescence-based assay; the imaging and verification of PHFs by negative stain transmission electron microscopy.

Alzheimer Disease↗
PubMed1999

[Objective audiologic assessment of children treated with amikacin].

Hearing assessment of 14 children suffered from urinary tract infection and treated by amikacin is reported. The dosage of amikacin was 7.5 mg/kg/daily for 10 days and the serum level of amikacin not exceeded the 35 mcg/ml. The aim of the study was on the one hand to determine the hearing damaging side effect of amikacin and on the other to assess the usefulness of objective methods for detection of hearing loss in this population. Authors used for screening a transient otoacoustic emission (TEOAE) during and after (2-4 weeks) therapy. If subjective and objective (TEOAE) methods gave a good result, no further checkup has considered as necessary, but if there were no evoked emission, acoustic brainstem response audiometry has been carried out for verification. It result no hearing loss could be detected in the measured specimen. In conclusion it has been stated that by proper dosage and serum level screening amikacin may no lead to hearing loss in children, and objective methods are valuable for hearing screening and monitoring of such population of children.

Adolescent↗
PubMed1991

Conversion operation Billroth II into Billroth I with jejunal interposition.

First, under consideration of the erroneous operative often techniques often found in patients with B II gastrectomy, all functional complaints of these patients should prompt the consultant to recommend conversion surgery. Secondly, all recurrent ulcerations, whether peptic or anastomositis, represent an indication for conversion surgery. Last but not least reconstruction of normal nutrition passage in an important indication for surgery in patients with B II gastrectomy, restoring near physiologic passage circumstances. Particularly grave in its consequences is the gastric stump carcinoma with its fateful and irrevocable course for patients with B II gastrectomy if regular gastroscopic and laboratory follow-up inspection do not take place (regardless of questionable operation indication). We recall a tragic case of a woman with B II gastrectomy who refused conversion surgery despite histologic verification of metaplasia, who died of gastric stump carcinoma a year later.

Anastomosis, Surgical↗