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PubMed2006

Measurements of density and sticking probability of CN(X(2)Sigma(+)) radicals by laser-induced fluorescence spectroscopy.

CN(X(2)Sigma(+)) radicals were produced by the decomposition of BrCN with the microwave discharge flow of Ar under the conditions of Ar pressure in the range of 0.40-0.70 Torr. The laser-induced fluorescence (LIF) spectra of the CN(A(2)Pi(i)-X(2)Sigma(+)), 4-0, 5-1, and 7-2 bands were observed, and their intensities were calibrated against Rayleigh-scattering intensity by Ar atoms, from which the CN(X(2)Sigma(+)) radical density (n(CN(X))) was determined as (0.67+/-0.25) x 10(18) to (4.42+/-0.83) x 10(18) m(-3). Hydrogenated amorphous carbon nitride (a-CN(x):H) films were formed by depositing the CN(X(2)Sigma(+)) radicals on Si substrates in the same reaction system as LIF. The sticking probability (s) of the CN(X(2)Sigma(+)) radicals onto the a-CN(x):H films was determined by using n(CN(X)), the flow speed, and the weight (w) of a-CN(x):H. The s value was determined as (6.4+/-6.4) x 10(-2) to (2.5+/-1.2) x 10(-2), where the errors are predominantly determined by those in n(CN(X)) and w. The procedure described in the present study will provide a methodology to determine the sticking probability of the precursor radicals of the film formation based on the gas-phase LIF spectroscopy.

Chemistry, Physical↗

PubMed2004

A simple method for computing exact probabilities of mutation numbers.

We describe a method for the recursive computation of exact probability distributions for the number of neutral mutations segregating in samples of arbitrary size and configuration. Construction of the recursions requires only characterization of evolutionary changes as a Markov process and determination of one-step transition matrices. We address the pattern of nucleotide diversity at a neutral marker locus linked to a determinant of mating type. Under a reformulation of parameters, the method also applies directly to metapopulation models with island migration among demes. Characterization of complete probability distributions facilitates parameter estimation and hypothesis testing by likelihood- as well as moment-based approaches.

Algorithms↗

PubMed2006

Separation of time scales, fixation probabilities and convergence to evolutionarily stable states under isolation by distance.

To a first order of approximation, selection is frequency independent in a wide range of family structured models and in populations following an island model of dispersal, provided the number of families or demes is large and the population is haploid or diploid but allelic effects on phenotype are semidominant. This result underlies the way the evolutionary stability of traits is computed in games with continuous strategy sets. In this paper similar results are derived under isolation by distance. The first-order effect on expected change in allele frequency is given in terms of a measure of local genetic diversity, and of measures of genetic structure which are almost independent of allele frequency in the total population when the number of demes is large. Hence, when the number of demes increases the response to selection becomes of constant sign. This result holds because the relevant neutral measures of population structure converge to equilibrium at a rate faster than the rate of allele frequency changes in the total population. In the same conditions and in the absence of demographic fluctuations, the results also provide a simple way to compute the fixation probability of mutants affecting various ecological traits, such as sex ratio, dispersal, life-history, or cooperation, under isolation by distance. This result is illustrated and tested against simulations for mutants affecting the dispersal probability under a stepping-stone model.

Ecology↗

PubMed2006

Probability of fixation under weak selection: a branching process unifying approach.

We link two-allele population models by Haldane and Fisher with Kimura's diffusion approximations of the Wright-Fisher model, by considering continuous-state branching (CB) processes which are either independent (model I) or conditioned to have constant sum (model II). Recent works by the author allow us to further include logistic density-dependence (model III), which is ubiquitous in ecology. In all models, each allele (mutant or resident) is then characterized by a triple demographic trait: intrinsic growth rate r, reproduction variance sigma and competition sensitivity c. Generally, the fixation probability u of the mutant depends on its initial proportion p, the total initial population size z, and the six demographic traits. Under weak selection, we can linearize u in all models thanks to the same master formula u = p + p(1 - p)[g(r)s(r) + g(sigma)s(sigma) + g(c)s(c)] + o(s(r),s(sigma),s(c), where s(r) = r' - r, s(sigma) = sigma-sigma' and s(c) = c - c' are selection coefficients, and g(r), g(sigma), g(c) are invasibility coefficients (' refers to the mutant traits), which are positive and do not depend on p. In particular, increased reproduction variance is always deleterious. We prove that in all three models g(sigma) = 1/sigma and g(r) = z/sigma for small initial population sizes z. In model II, g(r) = z/sigma for all z, and we display invasion isoclines of the 'mean vs variance' type. A slight departure from the isocline is shown to be more beneficial to alleles with low sigma than with high r. In model III, g(c) increases with z like ln(z)/c, and g(r)(z) converges to a finite limit L > K/sigma, where K = r/c is the carrying capacity. For r > 0 the growth invasibility is above z/sigma when z < K, and below z/sigma when z > K, showing that classical models I and II underestimate the fixation probabilities in growing populations, and overestimate them in declining populations.

Alleles↗

PubMed1969

Exclusion of protein from high polymer media. I. Derivation of probability distribution for the number of fiber centers within any sphere of radius r.

Ogston's (1958) fiber model based on Poisson's distribution function gives the average number of fibers making contact and no contact inside a sphere of radius r. The probability of penetration of spherical particles within a fibrous network was derived from the moment generating function [Formula: see text] A is the number of particles that intrude into a sphere of radious r. alpha(mu) is the probability that a particle, whose center is mu units away from the origin, intrudes into a sphere of radius r. A has a Poisson distribution with a mean value E(A) = 4pinualpha(mu)mu(2)dmu. The theoretical derivation of the distribution function of A gives Ogston's fiber model.

Biological Transport↗

PubMed1990

Direct measurement of the concentration- and time-dependent open probability of the nicotinic acetylcholine receptor channel.

Using the outside-out patch clamp recording technique together with a rapid solution exchange system, we measured ionic currents through nicotinic acetylcholine (ACh) receptor channels from BC3H-1 cells in response to rapid applications of 0.3-1,000 microM ACh. We used nonstationary fluctuation analysis of ensembles of responses to deduce the number of channels in the patch, the maximum open channel probability as a function of ACh concentration and the time course of a fast desensitization process. We found that: (a) Excised patches from BC3H-1 cells typically contain between 50 and 150 functional ACh receptor ion channels. (b) The open channel probability is proportional to [ACh]1.95 at low concentrations of ACh, is half-maximal at 20 microM ACh and saturates above 100 microM ACh. (c) ACh is a very efficacious agonist; 100 microM ACh opens at least 90% of the available channels. This estimate of efficacy is model-independent. (d) The rate of decay of the agonist-induced current is concentration-dependent. In the presence of 100 microM ACh the current decays with a time constant of 50-100 ms. It decays more slowly in the presence of lower concentrations of agonist but is relatively insensitive to voltage.

Animals↗

PubMed1995

Probability assessment of conformational ensembles: sugar repuckering in a DNA duplex in solution.

Conformational flexibility of molecules in solution implies that different conformers contribute to the NMR signal. This may lead to internal inconsistencies in the 2D NOE-derived interproton distance restraints and to conflict with scalar coupling-based torsion angle restraints. Such inconsistencies have been revealed and analyzed for the DNA octamer GTATAATG.CATATTAC, containing the Pribnow box consensus sequence. A number of subsets of distance restraints were constructed and used in the restrained Monte Carlo refinement of different double-helical conformers. The probabilities of conformers were then calculated by a quadratic programming algorithm, minimizing a relaxation rate-base residual index. The calculated distribution of conformers agrees with the experimental NOE data as an ensemble better than any single structure. A comparison with the results of this procedure, which we term PARSE (Probability Assessment via Relaxation rates of a Structural Ensemble), to an alternative method to generate solution ensembles showed, however, that the detailed multi-conformational description of solution DNA structure remains ambiguous at this stage. Nevertheless, some ensemble properties can be deduced with confidence, the most prominent being a distribution of sugar puckers with minor populations in the N-region and major populations in the S-region. Importantly, such a distribution is in accord with the analysis of independent experimental data--deoxyribose proton-proton scalar coupling constants.

Algorithms↗

PubMed2000

A sequence in the carboxy-terminus of the alpha(1C) subunit important for targeting, conductance and open probability of L-type Ca(2+) channels.

The role of the 80-amino acid motif 1572-1651 in the C-terminal tail of alpha(1C) Ca(2+) channel subunits was studied by comparing properties of the conventional alpha(1C,77) channel expressed in HEK-tsA201 cells to three isoforms carrying alterations in this motif. Replacement of amino acids 1572-1651 in alpha(1C,77) with 81 non-identical residues leading to alpha(1C,86) impaired membrane targeting and cluster formation of the channel. Similar to alpha(1C, 86), substitution of its 1572-1598 (alpha(1C,77L)) or 1595-1652 (alpha(1C,77K)) segments into the alpha(1C,77) channel yielded single-channel Ba(2+) currents with increased inactivation, reduced open probability and unitary conductance, when compared to the alpha(1C,77) channel. Thus, the C-terminal sequence 1572-1651 of the alpha(1C) subunit is important for membrane targeting, permeation and open probability of L-type Ca(2+) channels.

Amino Acid Sequence↗

PubMed1993

The pattern of the luteinizing hormone surge in spontaneous cycles is related to the probability of conception.

OBJECTIVE: To determine whether the pattern of the LH surge in a treatment cycle with artificial insemination with the husband's semen (AIH) because of cervical factor infertility is associated with the probability of conception. DESIGN: Retrospective study. SETTING: University Hospital, Department of Obstetrics and Gynecology. PATIENTS: Couples with cervical factor infertility as the main cause of subfertility. INTERVENTIONS: Luteinizing hormone monitored AIH. MAIN OUTCOME MEASURE: Whether or not a pregnancy occurred after AIH. RESULTS: There were 53 pregnancies in 382 IUI cycles (pregnancy rate [PR] per cycle: 13.9%). The PR was significantly higher in cycles with an LH surge of 2 days compared with cycles with a surge of 1 day. The probability of conception also seemed to be related to the height of the LH surge. CONCLUSION: The pattern of the LH surge in patients with cervical factor infertility is related to the outcome of a treatment with AIH.

Adult↗

PubMed1994

Comparison of the cumulative probability of pregnancy after in vitro fertilization-embryo transfer by infertility factor and age.

OBJECTIVE: To compare the cumulative probability of pregnancy after multiple IVF cycles by age and cause of infertility. DESIGN: A prospective study was done in which patients were followed from the time they registered for their first IVF cycle until they achieved a clinical pregnancy, withdrew from treatment, or study was terminated. PATIENTS, SETTING, TREATMENTS: Infertile women undergoing IVF-ET at the Cooper Institute for In Vitro Fertilization were enrolled in this study if the luteal phase leuprolide acetate (LA) and hMG controlled ovarian hyperstimulation (COH) regimen was used. MAIN OUTCOME MEASURES: Clinical pregnancy, as determined by a positive beta-hCG level and ultrasonographic confirmation of a gestational sac, and delivery rates based on number of women with live births were compared by infertility factor and age. RESULTS: The 3-month cumulative probability of pregnancy based on life table analysis was 33% in women with tubal factor who were < or = 35 years of age, 25% in women with tubal factor who were > 35 years of age, 30% for women with multiple factors who were < or = 35 years of age, and 14% for women with multiple factors who were > 35 years of age. The rate for the older women with multiple factors was significantly lower than that for the other groups. The delivery rates were lower for the women with multiple factors than for women under 35 with tubal factor only. CONCLUSIONS: There is a significant effect of age and infertility factor on pregnancy and delivery rates. Physicians should consider these factors in evaluating their patients' prospects for success in IVF-ET.

Adult↗

PubMed2000

The density of the extinction probability of a time homogeneous linear birth and death process under the influence of randomly occurring disasters.

Under the influence of randomly occurring disasters, the eventual extinction probability, q, of a birth and death process, Z, is a random variable. In this paper, we obtain an integral expression for the probability density function g(x) of q under the assumption that the population process Z is a time homogeneous linear birth and death process and the disasters occur according to an arbitrary renewal process so that its interarrival times have a density. An example is provided to demonstrate how to evaluate the integral numerically.

Birth Rate↗

PubMed2003

Probability of biochemical recurrence by analysis of pathologic stage, Gleason score, and margin status for localized prostate cancer.

OBJECTIVES: The Partin tables provide pretreatment information regarding the probability of various pathologic stages (eg, organ confined, extraprostatic extension, and seminal vesicle or lymph node involvement). Although the pathologic stage serves as an excellent surrogate for outcome after radical prostatectomy (RRP), many patients and physicians want to know how the predictions made from the Partin tables can be translated into long-term biochemical recurrence-free survival. In this work, we go beyond the pathologic outcomes predicted by the Partin nomograms to provide long-term biochemical recurrence-free estimates on the basis of the pathologic data obtained at RRP to help counsel patients after surgery for prostate cancer. METHODS: The study group comprised 1955 men treated by one surgeon with RRP and pelvic lymph node dissection for clinically localized disease (1989 to 2001). The patients were followed up for at least 1 year postoperatively, and the disease-free survival rates were determined using Kaplan-Meier analysis. RESULTS: The pathologic stages were as follows: organ confined in 57%, extraprostatic extension in 35%, seminal vesicle involvement in 4%, and lymph node involvement in 4%. The prostatectomy Gleason score distribution was as follows: 2 to 4 in 1%, 5 to 6 in 63%, 7 in 30%, and 8 to 10 in 6%. Overall, a positive surgical margin was present in 9.8%. On the basis of the prostatectomy Gleason score, pathologic stage, and surgical margin status, the probability of long-term biochemical recurrence-free survival was divided into four groups: excellent, good, moderate, and low. CONCLUSIONS: These simple to use and explain risk groups can be used to predict long-term biochemical recurrence-free survival from pathologic stage data obtained at surgery or predicted from the Partin tables, along with surgical margin status and Gleason score information obtained at RRP.

Adenocarcinoma↗

PubMed1984

Methotrexate systemic clearance influences probability of relapse in children with standard-risk acute lymphocytic leukaemia.

108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.

Bone Marrow Examination↗

PubMed2002

Probability of and risk factors for introduction of infectious diseases into Dutch SPF dairy farms: a cohort study.

A 2-year cohort study was conducted to investigate the probability of disease introduction into Dutch dairy farms. The farms were tested regularly for diseases and were visited biannually to collect management data. Ninety-five specific pathogen-free (SPF) dairy farms were selected from a database of bovine herpesvirus type 1 (BHV1)-free farms to study the probability of, and risk factors for, introduction of BHV1, bovine viral diarrhoea virus (BVDV), Salmonella enterica subsp. enterica serotype Dublin (S. dublin), and Leptospira interrogans serovar hardjo (L. hardjo). Although most of the 95 SPF farms had a low risk on introduction of infectious diseases, one disease was introduced into 12 farms and two diseases were introduced into one farm. Three farms experienced an outbreak of BHV1, one farm an outbreak of L. hardjo, two farms BVDV, six farms S. dublin, and one farm both BHV1 and S. dublin. The total incidence rate was 0.09 (0.06-0.12) per herd-year at risk. The results suggest that the "non-outbreak" farms were significantly more closed than the "outbreak" farms. Direct animal contacts with other cattle should be avoided and professional visitors should be instructed to wear protective clothing before handling cattle.

Animal Husbandry↗

PubMed2000

Cardiac and lung complication probabilities after breast cancer irradiation.

PURPOSE: To assess for locoregional irradiation of breast cancer patients, the dependence of cardiac (cardiac mortality) and lung (radiation pneumonitis) complications on treatment technique and individual patient anatomy. MATERIALS AND METHODS: Three-dimensional treatment planning was performed for 30 patients with left-sided breast cancer and various breast sizes. Two locoregional techniques (Techniques A and B) and a tangential field technique, including only the breast in the target volume, were planned and evaluated for each patient. In both locoregional techniques tangential photon fields were used to irradiate the breast. The internal mammary (IM)-medial supraclavicular (MS) lymph nodes were treated with an anterior mixed electron/photon field (Technique A) or with an obliquely incident mixed electron/photon IM field and an anterior electron/photon MS field (Technique B). The optimal IM and MS electron field dimensions and energies were chosen on the basis of the IM-MS lymph node target volume as delineated on CT-slices. The position of the tangential fields was adapted to match the IM-MS fields. Dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) for the heart and lung were compared for the three techniques. In the beam's eye view of the medial tangential fields the maximum distance of the heart contour to the posterior field border was measured; this value was scored as the Maximum Heart Distance. RESULTS: The lymph node target volume receiving more than 85% of the prescribed dose was on average 99% for both locoregional irradiation techniques. The breast PTV receiving more than 95% of the prescribed dose was generally smaller using Technique A (mean: 90%, range: 69-99%) than using Technique B (mean: 98%, range: 82-100%) or for the tangential field technique (mean: 98%, range: 91-100%). NTCP values for excess cardiac mortality due to acute myocardial ischemia varied considerably between patients, with minimum and maximum values of 0.1 and 7.5% (Technique A), 0.1 and 5.8% (Technique B) and 0.0 and 6.1% (tangential tech.). The NTCP values were on average significantly higher (P<0.001) by 1.7% (Technique A) and 1.0% (Technique B) when locoregional breast irradiation was given, compared with irradiation of the left breast only. The NTCP values for the tangential field technique could be estimated using the Maximum Heart Distance. NTCP values for radiation pneumonitis were very low for all techniques; between 0.0 and 1.0%. CONCLUSIONS: Technique B results in a good coverage of the breast and locoregional lymph nodes, while Technique A sometimes results in an underdosage of part of the target volume. Both techniques result in a higher probability of heart complications compared with tangential irradiation of the breast only. Irradiation toxicity for the lung is low in all techniques. The Maximum Heart Distance is a simple and useful parameter to estimate the NTCP values for cardiac mortality for tangential breast irradiation.

Breast Neoplasms↗

PubMed2002

Cardiac and pulmonary doses and complication probabilities in standard and conformal tangential irradiation in conservative management of breast cancer.

BACKGROUND AND PURPOSE: The clinical benefit of irradiating the intact breast after lumpectomy must be weighted against the risk of severe toxicity. We present a study on cardiac and pulmonary dose-volume data and the related complication probabilities of tangential breast irradiation having the following objectives: (1) to quantify the sparing of the organs at risk (ORs), the heart and the lung, achieved by three-dimensional (3-D) conformal tangential irradiation (CTI) as compared to standard tangential irradiation (STI); (2) to elucidate the uncertainty in radiation tolerance data; and (3) to analyse the relation between the amount of OR irradiated and the resulting morbidity risk. MATERIAL AND METHODS: Computed tomography (CT)-based 3-D treatment plans of 26 patients prescribed to CTI of the intact breast were applied. Contour-based STI has been our routine treatment, and was reconstructed for all patients. Dose-volume data and normal tissue complication probability (NTCP) predictions from the probit and relative seriality models with several cardiac and pulmonary tolerance parameterizations were analysed and compared. RESULTS AND CONCLUSIONS: A significant amount of normal tissues can be spared from radiation by using CT-based CTI, resulting in a 50% reduction of the average excess cardiac mortality risk in the left-sided cases. The risks for pericarditis and pneumonitis were too low to reveal any clinically significant difference between the treatments. For the STI set-up, a regression analysis showed that the excess cardiac mortality risk increased when larger parts of the heart were inside the fields. However, the different excess cardiac mortality and pneumonitis tolerance parameters resulted in statistically significant different NTCPs, which precluded the ability to accurately predict absolute NTCPs after tangential breast irradiation. Despite this uncertainty the different series of cardiac and pulmonary risk predictions were in relatively good agreement when small volumes of the ORs were irradiated. From the present data and without consideration of patient or organ motion, it therefore appears that tangential breast irradiation with less than 1 cm of the heart and 2-2.5 cm of the lung included inside the treatment fields will cause at most 1 per thousand risk for cardiac mortality and pulmonary morbidity. CT-based CTI should be considered, in particular for the left-sided cases, if these requirements cannot be met.

Adult↗

PubMed1998

Volume effects in the irradiated canine spinal cord: do they exist when the probability of injury is low?

PURPOSE: The purpose of this study was to investigate volume effects in the irradiated canine spinal cord. MATERIALS AND METHODS: Eighty-nine beagle dogs were given 44-84 Gy photons in 4 Gy fractions to 4 or 20 cm lengths of thoracic spinal cord. As controls, 36 dogs were given 60-84 Gy in 2 Gy fractions to a 20 cm length of spinal cord and six dogs were unirradiated. Dogs were evaluated for clinical signs, and after euthanasia, for occurrence of gross lesions, severe lesions of massive hemorrhage, white matter necrosis and/or parenchymal atrophy and mild lesions of focal fiber loss. White matter vacuoles, meningeal thickness and dorsal root ganglia lesions were quantified. Data were analyzed to test for an effect of volume on dose-response curves. RESULTS: Significant volume effects were found between 4 and 20 cm lengths of irradiated spinal cord for gross lesions, severe lesions and mild lesions (8.3-15.0 Gy difference at the ED50 level). The ED50 in 4 Gy fractions for severe lesions was 56.9 Gy (95% CI 53.1-60.6) for 20 cm and 68.8 Gy (95% CI 64.5-75.1) for 4 cm fields. Significant improvements in the fit of data to dose-response curves resulted when using models with either parallel or non-parallel curves, but in either case an appreciable difference existed between curves at low probabilities of injury. Volume effects were present for meningeal thickness and slopes of dose-response curves were different. Clinical signs correlated well with severe lesions for 20 cm (ED50 = 54.0 Gy), but not for 4 cm fields (ED50 = 77.6 Gy). CONCLUSIONS: Volume effects exist for the occurrence of pathologic lesions in irradiated canine spinal cord. Clinical compensation for pathologic lesions occur at small, but not large irradiated volumes. There is insufficient data to support a decreased slope of dose-response curves with decreased volume. Volume effects estimated at the 50% level of spinal cord injury could also hold at low probabilities of injury characteristic of the clinic.

Animals↗

PubMed2000

Mann-Whitney/Wilcoxon's nonparametric cumulative probability distribution.

It is demonstrated how complete nonparametric, cumulative probability distributions for Mann-Whitney/Wilcoxon's nonparametric, two-sample test can be constructed based on algorithms published earlier in this journal. These procedures provide cumulative probabilities for all possible rank sums in the nonparametric two-sample test. Separate programs for MS(PC)-DOS and Macintosh computers are offered.

Algorithms↗