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PubMed1990

Clinical considerations for neutron capture therapy of brain tumors.

The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues.

Animals↗

PubMed1992

Estimating the fraction of invariable codons with a capture-recapture method.

A codon-based approach to estimating the number of variable sites in a protein is presented. When first and second positions of codons are assumed to be replacement positions, a capture-recapture model can be used to estimate the number of variable codons from every pair of homologous and aligned sequences. The capture-recapture estimate is compared to a maximum likelihood estimate of the number of variable codons and to previous approaches that estimate the number of variable sites (not codons) in a sequence. Computer simulations are presented that show under which circumstances the capture-recapture estimate can be used to correct biases in distance matrices. Analysis of published sequences of two genes, calmodulin and serum albumin, shows that distance corrections that employ a capture-recapture estimate of the number of variable sites may be considerably different from corrections that assume that the number of variable sites is equal to the total number of positions in the sequence.

Biological Evolution↗

PubMed2006

A markerless motion capture system to study musculoskeletal biomechanics: visual hull and simulated annealing approach.

Human motion capture is frequently used to study musculoskeletal biomechanics and clinical problems, as well as to provide realistic animation for the entertainment industry. The most popular technique for human motion capture uses markers placed on the skin, despite some important drawbacks including the impediment to the motion by the presence of skin markers and relative movement between the skin where the markers are placed and the underlying bone. The latter makes it difficult to estimate the motion of the underlying bone, which is the variable of interest for biomechanical and clinical applications. A model-based markerless motion capture system is presented in this study, which does not require the placement of any markers on the subject's body. The described method is based on visual hull reconstruction and an a priori model of the subject. A custom version of adapted fast simulated annealing has been developed to match the model to the visual hull. The tracking capability and a quantitative validation of the method were evaluated in a virtual environment for a complete gait cycle. The obtained mean errors, for an entire gait cycle, for knee and hip flexion are respectively 1.5 degrees (+/-3.9 degrees ) and 2.0 degrees (+/-3.0 degrees ), while for knee and hip adduction they are respectively 2.0 degrees (+/-2.3 degrees ) and 1.1 degrees (+/-1.7 degrees ). Results for the ankle and shoulder joints are also presented. Experimental results captured in a gait laboratory with a real subject are also shown to demonstrate the effectiveness and potential of the presented method in a clinical environment.

Biomechanical Phenomena↗

PubMed2006

Underreporting of meningococcal disease incidence in the Netherlands: results from a capture-recapture analysis based on three registration sources with correction for false positive diagnoses.

In order to come to a reliable evaluation of the effectiveness of the chosen vaccination policy regarding meningococcal disease, the completeness of registrations on meningococcal disease in the Netherlands was estimated with the capture-recapture method. Data over 1993-1998 were collected from (A) mandatory notifications (n = 2926); (B) hospital registration (n = 3968); (C) laboratory surveillance (n = 3484). As the standard capture-recapture method does not take into account false positive diagnoses, we developed a model to adjust for the lack of specificity of our sources. We estimated that 1363 cases were not registered in any of the three sources in the period of study. The completeness of the three sources was therefore estimated at 49% for source A, 67% for source B and 58% for source C. After adjustment for false positive diagnoses, the completeness of source A, B, and C was estimated as 52%, 70% and 62%, respectively. The capture-recapture methods offer an attractive approach to estimate the completeness of surveillance sources and hence contribute to a more accurate estimate of the disease burden under study. However, the method does not account for higher-order interactions or presence of false positive diagnoses. Being aware of these limitations, the capture-recapture method still elucidates the (in)completeness of sources and gives a rough estimate of this (in)completeness. This makes a more accurate monitoring of disease incidence possible and hence attributes to a more reliable foundation for the design and evaluation of health interventions such as vaccination programs.

Disease Notification↗

PubMed1995

Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

OBJECTIVE: Our purpose was to determine the clinical value of human papillomavirus deoxyribonucleic acid testing with the hybrid capture test, specifically to examine whether human papillomavirus testing could identify which women with Papanicolaou smears read as atypical squamous cells of undetermined significance were most likely to have histologically confirmed cervical intraepithelial neoplasia. STUDY DESIGN: Hybrid capture testing for 14 human papillomavirus types, repeat Papanicolaou smears, and colposcopically directed biopsies were performed concurrently on 217 women referred to a student health colposcopy clinic with a previous Papanicolaou smear read as atypical squamous cells of undetermined significance. RESULTS: Human papillomavirus deoxyribonucleic acid positivity was associated with an eightfold increased likelihood of histologic confirmation of cervical intraepithelial neoplasia. The sensitivity of hybrid capture for any cervical intraepithelial neoplasia was 86% (43/50) and for grade 2 or 3 was 93% (14/15), whereas the corresponding values for the repeat Papanicolaou smear were 60% (30/50) and 73% (11/15), respectively. Moreover, high viral levels of human papillomavirus types known to be associated with cervical cancer were strongly predictive of high-grade cervical intraepithelial neoplasia. CONCLUSIONS: Testing for human papillomavirus deoxyribonucleic acid with hybrid capture appears to offer an effective means by which patients whose cervical Papanicolaou smears have been read as atypical squamous cells of undetermined significance could be triaged for colposcopy. In particular, sensitivity for high-grade cervical intraepithelial neoplasia could be maintained and specificity markedly improved by referring only those patients who had elevated levels of human papillomavirus deoxyribonucleic acid of cancer-associated viral types.

Adolescent↗

PubMed1984

The stability of prostatic acid phosphatase, as measured by a capture immunoenzyme assay.

A capture immunoenzyme assay (CIEA) for prostatic acid phosphatase (PAP) was developed and used to study the stability of this isoenzyme. Immunospecifically purified goat antibodies to PAP were covalently bound to special discs and used to capture the enzyme in serum samples in a weakly acidic medium during the first incubation (2 h) at 37 degrees C. The capture enzyme was then measured by its catalytic activity with p-nitrophenyl phosphate as substrate during the second incubation (1 h) at 37 degrees C. As much as 98% of the PAP in test specimens was captured and measured by this CIEA. The test results were expressed as enzymatic activity (U/l), extrapolated from a standard curve which was linear between 0.026 and 70 U/l. In test sera stored at 4 degrees C, the PAP was variably stable for 7 to 70 days, but the enzyme was quite stable in serum when stored at -20 degrees C for at least 156 days. At room temperature, when the sera were appropriately acidified, there was no loss of enzymatic activity for periods of 15 days, and in some cases, a large proportion of activity was still intact after 70 days. At 4 degrees C, as well as -20 degrees C, acidified serum and the partially purified PAP standard showed complete stability for at least 7 months. The CIEA reactivity of positive test specimens was inhibited by L(+)-tartaric acid, but not by cupric sulfate. The acid phosphatases of blood cell extracts were non-reactive in the CIEA procedure. The CIEA results of 224 serum samples from patients with and without prostate cancer correlated very well with those obtained by two direct enzymatic and two commercial RIA procedures, with correlation coefficients between 0.960 and 0.993, and diagnostic agreement between 86% and 100%.

Acid Phosphatase↗

PubMed1983

Differential response of pineal melatonin levels to light at night in laboratory-raised and wild-captured 13-lined ground squirrels (Spermophilus tridecemlineatus).

Pineal melatonin levels were compared in laboratory-raised or wild-captured 13-lined ground squirrels (Spermophilus tridecemlineatus) that were either exposed to 10 h of darkness at night or to light which had an irradiance of 400 microW/cm2. In laboratory-born squirrels the period of darkness was associated with a gradual rise in pineal melatonin levels with peak values being reached at 0200 h, 6 h after darkness onset. Thereafter, melatonin levels decreased and were back to low daytime levels by 0800 h, 2 h after light onset. The exposure of laboratory-raised animals to an irradiance of 400 microW/cm2 during the night totally prevented the nocturnal rise in pineal melatonin levels in these animals. In wild-captured ground squirrels the period of darkness at night was associated with a rapid rise in pineal melatonin such that by 2200 h, 2 h after lights out, peak melatonin values were already attained; additionally, melatonin levels remained high throughout the period of darkness but returned to daytime values by 0800 h. Exposure of wild-captured squirrels to a light irradiance of 400 microW/cm2 during the normal dark period was completely incapable of suppressing pineal melatonin levels. The difference in the sensitivity of the pineal gland of laboratory-raised and wild-captured ground squirrels may relate to their previous lighting history.

Animals↗

PubMed1987

Motion capture anisotropy.

Two uncorrelated random dot patterns were superimposed and alternated to produce dynamic incoherent noise. When a low spatial frequency sine wave grating was optically superimposed on this noise and moved in step with the alternation of the two frames, the incoherent motion was masked and all the dots were seen to adhere to the grating and to move with it as a single rigid sheet ("Motion Capture"). Over a wide range of displacements subjects could not discriminate uncorrelated noise which was "captured" from correlated noise patterns which moved physically in the same direction as the grating. In fact the motion signal from the low frequency grating was even strong enough to overcome signals from two correlated random dot patterns which moved in the opposite direction. Capture was not as strong if the direction of dot motion was orthogonal to the direction of grating motion. We conclude that in any dynamic visual scene the motion of certain salient features in the image tends to dominate our perceptual experience. The signal from low frequencies masks or inhibits the signal from the high frequencies. Since the latter now have no motion signal of their own they are assumed to move with the low frequencies. Thus, motion capture suggests an important biological role for long-range apparent motion: the process serves to preserve continuity of object identity while at the same time eliminating spurious motion signals that arise from finer image features. In this manner the visual system solves the "correspondence problem" without benefit from either computation or cognition.

Discrimination, Psychological↗

PubMed1993

The immunochemistry of sandwich ELISAs--VI. Greater than 90% of monoclonal and 75% of polyclonal anti-fluorescyl capture antibodies (CAbs) are denatured by passive adsorption.

Quantitative data are presented showing that the method most commonly used to immobilize antibodies in microtiter immunoassays functionally inactivates most of the antibodies. These results were collected using five affinity purified polyclonal antibodies (pAbs) and six monoclonal antibodies (mAbs) specific for fluorescein (FLU) as capture antibodies (CAbs). These CAbs were tested for their ability to capture FLU4.2-BSA after immobilization by passive adsorption, the Protein-Avidin-Biotin-Capture (PABC) system or using previously adsorbed anti-globulins. Results indicate that under optimal conditions, < 10% of monoclonal capture antibody equivalents (CAbeqv) and congruent to 22% of polyclonal CAbeqv remain functional after passive adsorption. Immobilization via the PABC system improved the performance of mAbs by more than five-fold but had less than a two-fold effect on pAbs. Many CAbs immobilized using an anti-globulin retained full activity including the ability to bind two molecules of FLU4.2-BSA/molecule of CAb. The latter result is not necessarily a recommendation for the use of anti-globulin immobilization, since the number of functional CAbeqv per well is not significantly greater than that which can be achieved using passive adsorption.

Adsorption↗

PubMed1982

A comparison of antibody capture radio- and enzyme immunoassays with immunofluorescence for detecting IgM antibody in infants with congenital rubella.

IgM antibody capture radioimmunoassay (MACRIA) and enzyme immunoassay (MACEIA) were compared with immunofluorescence (IF) for detecting specific IgM antibody in 99 sera from 76 infants with confirmed congenital rubella, and 61 sera from a comparative group of 59 infants who had miscellaneous abnormalities but in whom congenital rubella was not confirmed. All of 35 specimens collected from confirmed cases within 12 weeks of birth were positive by all three methods and all but one of 17 specimens collected after the age of 18 months were uniformly negative. At intermediate ages discrepancies occurred in 18 specimens, of which eight were positive and 10 negative by IF. Three of these 18 specimens were negative by both antibody capture procedures but showed weak fluorescence; the other 15 were negative by MACEIA, but positive by MACRIA which appears to be the more sensitive of the antibody capture methods. Sera from five infants in the comparative group were clearly positive by all three methods. These five infants were probably congenitally infected with rubella. Sera from the other 54 infants were negative, except for one that gave a weakly positive result by MACRIA alone. Antibody capture procedures offer several advantages over previous methods for detecting IgM antibody. Although MACRIA was found to be slightly more sensitive than MACEIA, the greater stability of the enzyme label, together with the possibility of both visual and quantitative assessment, could make MACEIA the method of choice for detecting rubella-specific IgM.

Antibodies, Viral↗

PubMed1985

Oxygen binding by the blood and hematological effects of capture stress in two big game-fish: mako shark and striped marlin.

Blood from capture-stressed striped marlin cannot be fully saturated with oxygen in the presence of lactic acid because of a substantial Root effect. Titration of blood to pH 7.6 at 25 degrees C gave an O2 affinity constant, P50 = 17 mmHg. The P50 was highly sensitive to pH showing a Bohr factor phi = delta log P50/delta pH = -0.74. Blood from capture-stressed mako sharks did not show either a Root effect or a significant Bohr effect (delta log P50/delta pH = +0.16). The O2-affinity constant, P50, was 10.6 mmHg at pH 7.6 and 25 degrees C. Hematological measurements following capture gave hematocrit values of 24.2 +/- 8.1% and 32.3 +/- 10.8% for marlin and mako respectively, and high concentrations of blood lactate in both species (15-16 mmol l-1). The O2 transport properties of the blood are discussed in relation to oxygen demand and capture stress.

Animals↗

PubMed1982

Pinocytosis of poly (alpha, beta-(N-2-hydroxyethyl))-DL-aspartamide and a tyramine derivative by rat visceral yolk sacs cultured in vitro. Ability of phenolic residues to enhance the rate of pinocytic capture of a macromolecule.

Incorporation of 20% tyramine residues into its structure greatly increased the rate of pinocytosis of poly(alpha, beta-(N-2-hydroxyethyl))-DL-aspartamide (PHEA) by rat visceral yolk sacs cultured in vitro. Both the parent macromolecule and the tyramine derivative (PHEA-tyramine) were captured by adsorptive pinocytosis, the higher affinity of the derivative for the yolk sac plasma membrane being responsible for its greater rate of capture. Using 125I-labelled PHEA-tyramine, the relationship between substrate concentration and rate of capture was determined, it was also shown that following internalization, the PHEA-tyramine linkage is resistant to intracellular hydrolysis. Fluorescence micrographs were consistent with capture of both substrates being by pinocytosis and illustrated the highly efficient concentration of the tyramine derivative by yolk sac endodermal cells.

Animals↗

PubMed2005

Spore and micro-particle capture on an immunosensor surface in an ultrasound standing wave system.

The capture of Bacillus subtilis var. niger spores on an antibody-coated surface can be enhanced when that coated surface acts as an acoustic reflector in a quarter wavelength ultrasonic (3 MHz) standing wave resonator. Immunocapture in such a resonator has been characterised here for both spores and 1 microm diameter biotinylated fluorescent microparticles. A mean spatial acoustic pressure amplitude of 460 kPa and a frequency of 2.82 MHz gave high capture efficiencies. It was shown that capture was critically dependent on reflector thickness. The time dependence of particle deposition on a reflector in a batch system was broadly consistent with a calculated time of 35 s to bring 95% of particles to the coated surface. A suspension flow rate of 0.1 ml/min and a reflector thickness of 1.01 mm gave optimal capture in a 2 min assay. The enhancement of particle detection compared with the control (no ultrasound) situation was x 70. The system detects a total of five particles in 15 fields of view in a 2 min assay when the suspending phase concentration was 10(4) particles/ml. A general expression for the dependence of minimum concentration detectable on; number of fields examined, sample volume flowing through the chamber and assay time shows that, for a practical combination of these variables, the threshold detection concentration can be two orders of magnitude lower.

Bacillus subtilis↗

PubMed2005

Random aneuploidy and telomere capture in chronic lymphocytic leukemia and chronic myeloid leukemia patients.

Telomeric regions of the human genome are of particular interest, because rearrangements of these regions are difficult to identify by conventional chromosome banding technology. With the advent of molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH), it has been possible to investigate the terminus in cytogenetically visible terminal deletions and telomere rearrangements. We investigated telomere capture and aneuploidy rates in chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) patients, as well as in healthy control subsets. Using a FISH technique, we estimated the random aneuploidy and telomere capture of the 21q22, SNRPN, and 15qter loci. Higher aneuploidy rates were found in the leukocytes of CLL and CML patients, compared with the control group, for the 21q22 and SNRPN loci. There was no difference in the aneuploidy rate between the CML and CLL groups. Telomere capture was found in the two groups (CLL and CML), but not in the control group. We propose that the telomere capture phenomenon is much more common than has been reported in the literature; however, its prognostic significance is yet to be established.

Aged↗

PubMed2005

Toward a general mechanism of electron capture dissociation.

The effects of positive charge on the properties of ammonium and amide radicals were investigated by ab initio and density functional theory calculations with the goal of elucidating the energetics of electron capture dissociation (ECD) of multiply charged peptide ions. The electronic properties of the amide group in N-methylacetamide (NMA) are greatly affected by the presence of a remote charge in the form of a point charge, methylammonium, or guanidinium cations. The common effect of the remote charge is an increase of the electron affinity of the amide group, resulting in exothermic electron capture. The N-Calpha bond dissociation and transition state energies in charge-stabilized NMA anions are 20-50 kJ mol(-1) greater than in the hydrogen atom adduct. The zwitterions formed by electron capture have proton affinities that were calculated as 1030-1350 kJ mol(-1), and are sufficiently basic for the amide carbonyl to exothermically abstract a proton from the ammonium, guanidinium and imidazolium groups in protonated lysine, arginine, and histidine residues, respectively. A new mechanism is proposed for ECD of multiply charged peptide and protein cations in which the electron enters a charge-stabilized electronic state delocalized over the amide group, which is a superbase that abstracts a proton from a sterically proximate amino acid residue to form a labile aminoketyl radical that dissociates by N-Calpha bond cleavage. This mechanism explains the low selectivity of N-Calpha bond dissociations induced by electron capture, and is applicable to dissociations of peptide ions in which the charge carriers are metal ions or quaternary ammonium groups. The new amide superbase and the previously proposed mechanisms of ECD can be uniformly viewed as being triggered by intramolecular proton transfer in charge-reduced amide cation-radicals. In contrast, remote charge affects N-H bond dissociation in weakly bound ground electronic states of hypervalent ammonium radicals, as represented by methylammonium, CH3NH3*, but has a negligible effect on the N-H bond dissociation in the strongly bound excited electronic states. This refutes previous speculations that loss of "hot hydrogen" can occur from an excited state of an ammonium radical.

Acetamides↗

PubMed2006

Side-chain fragmentation of alkylated cysteine residues in electron capture dissociation mass spectrometry.

The recent development of novel fragmentation processes based on either electron capture directly or transfer from an anion show great potential for solving problems in proteomics that are intractable by the more widely employed thermal-based fragmentation processes such as collision induced dissociation. The dominant fragmentation occurring upon electron capture dissociation of peptides is cleavage of N-C alpha bonds in the peptide backbone to form c and z* ions. In the case of disulfide-linked peptides, it has also been shown that electron capture on one of the cystine sulfur atoms is favored, resulting in cleavage of the disulfide bond. In this study, we report that electron capture on the sulfur of alkylated cysteine residues is also a dominant process, causing cysteine side-chain loss from z* ions.

Alkylation↗

PubMed2004

Particle capture processes and evaporation on a microscopic scale in wet filters.

This paper details results of an experimental study of the capture of solid and liquid aerosols on fibrous filters wetted with water. A microscopic cell containing a single fibre (made from a variety of materials) was observed via a microscope, with a high speed CCD camera used to dynamically image the interactions between liquid droplets, zeolite and PSL particles and fibres. Variable quantities of liquid irrigation were used, and the possibility for subsequent fibre regeneration after clogging or drying was also studied. It was found that drainage of the wetting liquid (water) from the fibres occurred, even at very low irrigation rates when the droplet consisted almost completely of captured particles. It was also found that the fibre was rapidly loaded with captured particles when the irrigation was not supplied. However, almost complete regeneration (removal of the collected cake) by the liquid droplets occurred shortly after recommencement of the water supply. The study also examined the capture of oily liquid aerosols on fibres wetted with water. A predominance of the barrel shaped droplet on the fibre was observed, with oil droplets displacing water droplets (if the oil and fibre combination created a barrel shaped droplet), creating various compound droplets of oil and water not previously reported in literature. This preferential droplet shape implies that whatever the initial substance wetting a filter, a substance with a greater preferential adherence to the fibre will displace the former one.

Journal Article↗

PubMed2006

Probabilistic study of well capture zones distribution at the Lauswiesen field site.

The delineation of well capture zones is of utmost environmental and engineering relevance as pumping wells are commonly used both for drinking water supply needs, where protection zones have to be defined, and for investigation and remediation of contaminated aquifers. We analyze the probabilistic nature of well capture zones within the well field located at the "Lauswiesen" experimental site. The test site is part of an alluvial heterogeneous aquifer located in the Neckar river valley, close to the city of Tübingen in South-West Germany. We explore the effect of different conceptual models of the structure of aquifer heterogeneities on the delineation of three-dimensional probabilistic well catchment and time-related capture zones, in the presence of migration of conservative solutes. The aquifer is modeled as a three-dimensional, doubly stochastic composite medium, where distributions of geo-materials and hydraulic properties are uncertain. We study the relative importance of uncertain facies geometry and uncertain hydraulic conductivity and porosity on predictions of catchment and solute time of travel to the pumping well by focusing on cases in which (1) the facies distribution is random, but the hydraulic properties of each material are fixed, and (2) both facies geometry and material properties vary stochastically. The problem is tackled within a conditional numerical Monte Carlo framework. Results are provided in terms of probabilistic demarcations of the three-dimensional well catchment and time-related capture zones. Our findings suggest that the uncertainty associated with the prediction of the location of the outer boundary of well catchment at the "Lauswiesen" site is significantly affected by the conceptual model adopted to incorporate the heterogeneous nature of the aquifer domain in a predictive framework. Taking into account randomness of both lithofacies distribution and materials hydraulic conductivity allows recognizing the existence of preferential flow paths that influence the extent of the well catchment and the solute travel time distribution at the site.

Computer Simulation↗