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PubMed2003

Comparison of two Xanthomonas campestris pathovar campestris genomes revealed differences in their gene composition.

For the Xanthomonas campestris pathovar campestris wild-type strain B100 a plasmid-based clone library was constructed. The plasmids carried chromosomal fragments of 3-4 kb in size that were tagged in vitro with the artificial transposon KAN-2. More than 3000 of the transposon target sites were characterized by DNA sequencing. The sequences obtained were compared to the recently published genome of Xanthomonas campestris pathovar campestris strain ATCC 33913. Most of the sequenced clones derived from strain B100 matched the chromosomal sequence of strain ATCC 33913. An alignment to the circular map of this chromosome revealed that the similarities were statistically distributed over the entire genome of strain ATCC 33913. The similarity was obvious for protein coding sequences, as well as for mobile genetic elements. However, four regions in the genome of Xanthomonas campestris pathovar campestris strain ATCC 33913, ranging in size from 11 to 37 kb, were not represented in the sequenced clone library of Xanthomonas campestris pathovar campestris strain B100. On the other hand, 1.2% of the sequenced clones originating from Xanthomonas campestris pathovar campestris strain B100 showed no or insignificant similarities to the genome of strain ATCC 33913.

Chromosome Mapping↗

PubMed2005

Influence of surface and heat treatments on the flexural strength of Y-TZP dental ceramic.

OBJECTIVE: The aim of the investigation was to assess the influence of sandblasting, grinding, grinding orientation, polishing and heat treatment on the flexural strength of a yittria stabilized tetragonal zirconia polycrystals ceramic (Y-TPZ). METHODS: The specimens (160 beams) were equally divided into four groups according to the surface treatment (sandblasted, polished, ground parallel to the tensile axis, ground perpendicular). Twenty specimens from each group underwent heat treatment under the firing conditions used to fire a layer of porcelain and glaze. After treatment, the three-point flexure test was used to calculate the flexural strength and X-ray diffraction analysis was used to estimate the relative amount of monoclinic phase. The reliability of strength was assessed through the Weibull distribution. Statistical analysis was conducted with multiple regression analysis, one-way ANOVA and Tukey's pairwise multiple comparisons. Treated and fractured surfaces were observed with SEM. RESULTS: The following values of strength and relative content of monoclinic phase of zirconia were measured for each group: sandblasted (1540MPa; 9.5%); ground parallel (1330MPa; 8.3%); ground perpendicular (1525MPa; 8.3%); ground parallel and heated (1225MPa; monoclinic content not detectable); ground perpendicular and heated (1185MPa; monoclinic content not detectable); polished and heated (1165MPa; monoclinic content not detectable); polished (1095MPa; 0.8%); sandblasted and heated (955MPa; 0.3%). CONCLUSIONS: The present study suggests that sandblasting and grinding may be recommended to increase the strength of dental Y-TZP, provided they are not followed by heat treatment. Fine polishing may remove the layer of compressive stresses and therefore, lower the mean flexural strength.

Analysis of Variance↗

PubMed2006

Large hydrocarbon fuel pool fires: physical characteristics and thermal emission variations with height.

In a recent paper [P.K. Raj, Large LNG fire thermal radiation-modeling issues and hazard criteria revisited, Process Safety Progr., 24 (3) (2005)] it was shown that large, turbulent fires on hydrocarbon liquid pools display several characteristics including, pulsating burning, production of smoke, and reduced thermal radiation, with increasing size. In this paper, a semi-empirical mathematical model is proposed which considers several of these important fire characteristics. Also included in this paper are the experimental results for the variation of the fire radiance from bottom to top of the fire (and their statistical distribution) from the largest land spill LNG pool fire test conducted to date. The purpose of the model described in this paper is to predict the variation of thermal radiation output along the fire plume and to estimate the overall thermal emission from the fire as a function its size taking into consideration the smoke effects. The model utilizes experimentally measured data for different parameters and uses correlations developed from laboratory and field tests with different fuels. The fire dynamics and combustion of the fuel are modeled using known entrainment and combustion efficiency parameter values. The mean emissive power data from field tests are compared with model predictions. Model results for the average emissive powers of large, hypothetical LNG fires are indicated.

Fires↗

PubMed2006

A mathematical model of the treatment and survival of patients with high-grade brain tumours.

More years of life per patient are lost as the result of primary brain tumours than any other form of cancer. The most aggressive of these is known as glioblastoma (GBM). The median survival time of patients with GBM is under 10 months and the outlook has hardly improved over the past 20 years. Generally, these tumours are remarkably resistant to radiotherapy and yet about 2-3% of all GBMs appear to be cured. The objectives of this study were to formulate a mathematical and phenomenological model of tumour growth in a population of patients with GBM to predict survival, and to use the model to extract biological information from clinical data. The model describes the growth of the tumour and the resulting damage to the normal brain using simple concepts borrowed from chemical reaction engineering. Death is assumed to result when the amount of surviving normal brain falls to a critical level. Radiotherapy is assumed to destroy tumour but not healthy brain. Simple rules are included to represent approximately the clinician's decisions about what type of treatment to offer each patient. A population of patients is constructed by assuming that key parameters can be sampled from statistical distributions. Following Monte Carlo simulation, the model can be fitted to data from clinical trials. The model reproduces clinical data extremely accurately. This suggests that the long-term survivors are not a separate sub-population but are the 'lucky tail' of a unimodal distribution. The estimated values of radiation sensitivity (represented as SF2, the survival fraction after 2Gy) suggest the presence of severe hypoxia, which renders cells less sensitive to radiation. The model can predict the probable age distribution of tumours at presentation. The model shows the complicated effects of waiting times for treatment on the survival outcomes, and is used to predict the effects of escalation of radiotherapy dose. The model may aid the design of clinical trials using radiotherapy for patients with GBM, especially in helping to estimate the size of trial required. It is also designed in a generic form, and might be applicable to other tumour types.

Age Distribution↗

PubMed2004

Feature characterization in fMRI data: the Information Bottleneck approach.

Clustering is a well-known technique for the analysis of Functional Magnetic Resonance Imaging (fMRI) data, whose main advantage is certainly flexibility: given a metric on the dataset, it "summarizes" the main characteristics of the data. But intrinsic to this approach are also the problem of defining correctly the quantization accuracy, and the number of clusters necessary to describe the data. The Information Bottleneck (IB) approach to vector quantization, proposed by Bialek and Tishby, addresses these difficulties: (1) it deals with an explicit trade-off between quantization and data fidelity; (2) it does so during the clustering procedure and not post hoc; (3) it takes into account the full statistical distribution of the features within the feature space and not only their most likely value; last, it is principled through an information theoretic formulation, which is relevant in many situations. In this paper, we present how to benefit from this method to analyze fMRI data. Our application is the clustering of voxels according to the magnitude of their responses to several experimental conditions. The IB quantization provides a consistent representation of the data, allowing for an easy interpretation and comparison of datasets.

Algorithms↗

PubMed2006

Age dependent and cellular origin (stem versus progenitor) of a selected group of spontaneous brain tumors in humans.

The origin of spontaneous human brain tumors has been recently debated as originating from a stem rather than a progenitor cell. Based on the statistical distribution of a selected group of primary brain tumors, and on the clonality and field theory for cancer growth, we propose as plausible the contribution of progenitor cells in the origin of the most common brain tumors such as, pediatric, mixed (glial and neuronal), and the aggressive glioblastoma multiforme in adults. Operationally, stem cell is defined as having a renewal probability of p=1, a progenitor 0<p<1, and a terminally differentiated cell as p=0. The space-time field location (microenvironment, cell-cell interactions...) and mitotic potential of a cell limits the distinguishability between stem and progenitors, due to the interconvertibility of these states via the process of retrodifferentiation (dedifferentiation). If excessively iterated retrodifferentiation of a mitotically competent cell prompts such a cell to organize programs that are atypical vis-à-vis the standard ones. Regarding specifically malignant cells, aperiodic cycles of dedifferentiation favour emergence of subclonal populations whose anachronistic evolution might become idiosyncratically resistant to therapies previously efficient against the initial tumoral mass. Unfortunately the "ab initio" identification of such subclonal "drifters" is impaired by systematic uncertainties as quali-quantified in appendix.

Aging↗

PubMed2006

Body surface area in normal-weight, overweight, and obese adults. A comparison study.

Values for body surface area (BSA) are commonly used in medicine, particularly to calculate doses of chemotherapeutic agents and index cardiac output. Various BSA formulas have been developed over the years. The DuBois and DuBois (Arch Intern Med 1916;17:863-71) BSA equation is the most widely used, although derived from only 9 subjects. More recently, Mosteller (N Engl J Med 1987;317:1098) produced a simple formula, [weight (kg) x height (cm)/3600](1/2), which could be easily remembered and evaluated on a pocket calculator, but validation data in adults are rare. The purpose of the present study was to examine the BSA based on Mosteller's formula in normal-weight (body mass index [BMI], 20-24.9 kg/m(2)), overweight (BMI, 25-29.9 kg/m(2)), and obese (BMI, >/=30 kg/m(2)) adults (>18 years old) in comparison with other empirically derived formulas (DuBois and DuBois, Boyd [The growth of the surface area of the human body. Minneapolis: University of Minnesota Press; 1935], Gehan and George [Cancer Chemother Rep 1970;54:225-35], US Environmental Protection Agency [Development of statistical distributions or ranges of standard factors used in exposure assessments Washington, EPA/600/8-85-010. Office of Health and Environmental Assessment; 1985), Haycock et al [J Pediatr 1978;93:62-6], Mattar [Crit Care Med 1989;17:846-7], Livingston and Scott [Am J Physiol Endocrinol Metab 2001;281:E586-91]) and with the new 3-dimensional-derived formula of Yu et al (Appl Ergon. 2003;34:273-8). One thousand eight hundred sixty-eight patients were evaluated (397 normal weight [BMI, 23 +/- 1 kg/m(2); age, 50 +/- 14 years; M/F, 289/108], 714 overweight [BMI, 27 +/- 1 kg/m(2); age, 52 +/- 11 years; M/F, 594/120], and 757 obese [BMI, 36 +/- 6 kg/m(2); age, 53 +/- 11 years; M/F, 543/215]). The overall BSA was 2.04 +/- 0.24 m(2): 1.81 +/- 0.19 m(2) in normal-weight, 1.99 +/- 0.16 m(2) in overweight, and 2.21 +/- 0.22 m(2) in obese subjects. These values were significantly higher in overweight and obese patients compared with the values using the DuBois-DuBois formula (overall, 2.00 +/- 0.22 m(2), P < .01; normal weight, 1.81 +/- 0.19 m(2), P = .93; overweight, 1.97 +/- 0.16 m(2), P < .01; obese, 2.14 +/- 0.21 m(2), P < .001). We could show an excellent correlation between the results obtained from each formula, with all correlations of 0.97 or higher (between 0.971 and 0.999). Body surface area prediction with the commonly used DuBois formula underestimated BSA in obese patients by as much as 3% (male) to 5% (female). Based on the formula of Yu et al, however, BSA is overestimated when these traditional formulas are used. Although Mosteller's formula is recommended based on its simplicity and suitability for laboratory and clinical work in adults, accuracy studies in whites with 3-dimensional one-pass whole-body scanning are needed.

Adult↗

PubMed1996

Worker exposures to inhalable and total aerosol during nickel alloy production.

This paper describes a study that was carried out at a North American nickel alloy production facility to compare the levels of personal exposures to inhalable and total nickel-containing aerosols. It is part of a large body of work aimed at assessing the impact of introducing new personal sampling instrumentation with performance consistent with the latest criteria proposed by the International Standards Organization (ISO), the Comité Européen Normalisation (CEN) and the American Conference of Governmental Industrial Hygienists (ACGIH). Side-by-side sampling using the 37-mm filter holder (for total aerosol) and the so-called IOM inhalable aerosol sampler was conducted for the personal exposures of workers in a range of workplaces throughout the facility. The results showed that inhalable aerosol exposure levels-for both overall aerosol and for total nickel-were consistently and significantly higher than the corresponding total aerosol levels. Weighted least-squares linear regression yielded factors ranging from about 1.3 to 2.4 for overall dust and from about 1.5 to 3.5 for nickel. Inspection of the statistical distribution of the exposures for the whole plant suggested that it was log-normal.

Aerosols↗

PubMed2001

Stochastic simulation of hemagglutinin-mediated fusion pore formation.

Studies on fusion between cell pairs have provided evidence that opening and subsequent dilation of a fusion pore are stochastic events. Therefore, adequate modeling of fusion pore formation requires a stochastic approach. Here we present stochastic simulations of hemagglutinin (HA)-mediated fusion pore formation between HA-expressing cells and erythrocytes based on numerical solutions of a master equation. The following elementary processes are taken into account: 1) lateral diffusion of HA-trimers and receptors, 2) aggregation of HA-trimers to immobilized clusters, 3) reversible formation of HA-receptor contacts, and 4) irreversible conversion of HA-receptor contacts into stable links between HA and the target membrane. The contact sites between fusing cells are modeled as superimposed square lattices. The model simulates well the statistical distribution of time delays measured for the various intermediates of fusion pore formation between cell-cell fusion complexes. In particular, these are the formation of small ion-permissive and subsequent lipid-permissive fusion pores detected experimentally (R. Blumenthal, D. P. Sarkar, S. Durell, D. E. Howard, and S. J., J. Cell Biol. 135:63-71). Moreover, by averaging the simulated individual stochastic time courses across a larger population of cell-cell-complexes the model also provides a reasonable description of kinetic measurements on lipid mixing in cell suspensions (T. Danieli, S. L. Pelletier, Y.I. Henis, and J. M. White, 1996, J. Cell Biol. 133:559-569).

Cell Fusion↗

PubMed1985

Distribution of mass in relaxed frog skeletal muscle and its redistribution upon activation.

Five orders of equatorial reflection were recorded from both relaxed and fully activated intact frog sartorius muscle using synchrotron x-ray radiation. Electron density maps of the myofilament lattice in axial projection were calculated from the integrated intensities by Fourier synthesis, using all possible phase combinations. These maps were evaluated systematically in terms of their compatibility with electron microscopically and biochemically derived properties of the lattice structure and with the minimum wavelength principle. For the relaxed state, one phase combination emerged as most consistent with these constraints: it shows a thick filament with a compact core surrounded by an annular shell of density. The distribution of mass suggests that the S-2 moiety of the myosin molecule is an integral part of the thick-filament backbone and the S-1 moiety makes up the shell and is tilted or slewed around the backbone. For the active state, there are two feasible maps, which differ according to whether or not the activation process is associated with phase inversion in two of the reflections. Both maps represent patterns of redistribution of mass upon activation in which the thick-filament backbone is practically unaffected and there is movement of density from the annular shell towards the thin filaments. In addition to this outward radial flux of density from the thick-filament periphery, the pattern of net mass transfer involves a pronounced azimuthal component in both cases. The total net mass transfer is equivalent to approximately 20% (no phase change) or approximately 40% (with phase change) of the S-1 mass. From the observed systematic increase in peak widths of the higher orders, the size of the crystalline domain in the myofilament lattice in the relaxed sartorius is estimated to be greater than 650 nm and the variations in myofilament lattice spacing among different myofibrils to be about +/- 3%. Furthermore, in the activated state, the equilibrium positions of the myofilaments are no longer well ordered, but are distributed statistically about the lattice points with a standard deviation of approximately 3 nm.

Animals↗

PubMed1999

The lifetime of insulin hexamers.

The kinetic stability of insulin hexamers containing two metal ions was investigated by means of hybridization experiments. Insulin was covalently labeled at the N(epsilon)-amino group of Lys(B29) by a fluorescence donor and acceptor group, respectively. The labels neither affect the tertiary structure nor interfere with self-association. Equimolar solutions of pure donor and acceptor insulin hexamers were mixed, and the hybridization was monitored by fluorescence resonance energy transfer. With the total insulin concentration remaining constant and the association/dissociation equilibria unperturbed, the subunit interchange between hexamers is an entropy-driven relaxation process that ends at statistical distribution of the labels over 16 types of hexamers differing by their composition. The analytical description of the interchange kinetics on the basis of a plausible model has yielded the first experimental values for the lifetime of the hexamers. The lifetime is reciprocal to the product of the concentration of the exchanged species and the interchange rate constant: tau = 1/(c. k). Measured for different concentrations, temperatures, metal ions, and ligand-dependent conformational states, the lifetime was found to cover a range from minutes for T(6) to days for R(6) hexamers. The approach can be used under an unlimited variety of conditions. The information it provides is of obvious relevance for the handling, storage, and pharmacokinetic properties of insulin preparations.

Animals↗

PubMed1997

On periodic curvature and standing wave motions in cell membranes.

Cell membranes can form cubic arrangements and there is evidence for the occurrence of periodic curvature in simple membranes. The periodicity of the bilayer implies a standing wave character of vibrational motions. It is proposed that the periodic curvature reflects a dominating mode of standing wave oscillations, with the different cubic bilayer structures representing alternative standing wave conformations of the bilayer. The wave motions in lamellar liquid-crystalline phases, as well as in vesicles and membranes, which lack lateral periodicity, are known to exhibit statistically distributed undulations. The standing wave character of conformational fluctuations of periodically curved membranes, on the other hand, results in an organisation in time and space. Calculated models of standing wave conformations of membranes are demonstrated, and functional aspects of such biomembranes are discussed.

Cell Membrane↗

PubMed2000

Cross-cultural music cognition: cognitive methodology applied to North Sami yoiks.

This article is a study of melodic expectancy in North Sami yoiks, a style of music quite distinct from Western tonal music. Three different approaches were taken. The first approach was a statistical style analysis of tones in a representative corpus of 18 yoiks. The analysis determined the relative frequencies of tone onsets and two- and three-tone transitions. It also identified style characteristics, such as pentatonic orientation, the presence of two reference pitches, the frequency of large consonant intervals, and a relatively large set of possible melodic continuations. The second approach was a behavioral experiment in which listeners made judgments about melodic continuations. Three groups of listeners participated. One group was from the Sami culture, the second group consisted of Finnish music students who had learned some yoiks, and the third group consisted of Western musicians unfamiliar with yoiks. Expertise was associated with stronger veridical expectations (for the correct next tone) than schematic expectations (based on general style characteristics). Familiarity with the particular yoiks was found to compensate for lack of experience with the musical culture. The third approach simulated melodic expectancy with neural network models of the self-organizing map (SOM) type (Kohonen, T. (1997). Self-organizing maps (2nd ed.). Berlin: Springer). One model was trained on the excerpts of yoiks used in the behavioral experiment including the correct continuation tone, while another was trained with a set of Finnish folk songs and Lutheran hymns. The convergence of the three approaches showed that both listeners and the SOM model are influenced by the statistical distributions of tones and tone sequences. The listeners and SOM models also provided evidence supporting a core set of psychological principles underlying melody formation whose relative weights appear to differ across musical styles.

Adult↗

PubMed1999

Strong hydrophobic nature of cysteine residues in proteins.

The differences between disulfide-bonding cystine (Cys_SS) and free cysteine (Cys_SH) residues were examined by analyzing the statistical distribution of both types of residue in proteins of known structure. Surprisingly, Cys_SH residues display stronger hydrophobicity than Cys_SS residues. A detailed survey of atoms which come into contact with the sulfhydryl group (sulfur atom) of Cys_SH revealed those atoms are essentially the same in number and variety as those of the methyl group of isoleucine, but are quite different to those of the hydroxyl group of serine. Moreover, the relationships among amino acids were also determined using the 3D-profile table of known protein structures. Cys_SH was located in the hydrophobic cluster, along with residues such as Met, Trp and Tyr, and was clearly separated from Ser and Thr in the polar cluster. These results imply that free cysteines behave as strongly hydrophobic, and not hydrophilic, residues in proteins.

Algorithms↗

PubMed1996

Dose timing in tumor radiotherapy: considerations of cell number stochasticity.

A typical tumor radiotherapy regimen using external beam X rays consists of doses on weekdays for 4-7 weeks. During the final weeks, the tumor may contain only a few cells capable of regenerating the tumor and may be growing exponentially between doses. Stochastic fluctuations of the cell number can influence the optimal time pattern of dose delivery. If the total dose is fixed, a deterministic model of exponential tumor growth, neglecting stochastic effects, predicts that the way the radiation dose is spread out in time does not affect the average number of tumor cells at the end. However, we here show, within the framework of a birth-death model, that when stochastics are taken into account, the earlier the dose is given (consistent with other constraints imposed by quite different considerations), the better. The proof uses a transformation that simplifies the characteristic equation of the partial differential equation governing the probability generating function for a birth-death process with time-dependent rates. The theorem that earlier is better holds for any statistical distribution of cell number from patient to patient at the start of the exponential growth phase and for virtually any cell-killing model. Numerical results indicate the stochastic effects, although not dominant, are not negligible.

Cell Count↗

PubMed2002

Is implicit learning spared in amnesia? Rule abstraction and item familiarity in artificial grammar learning.

We examined implicit learning of an artificial grammar in amnesic and control participants. The "biconditional" grammar used to generate study and test strings allows two potential sources of judgements in artificial grammar learning to be unconfounded: participants could either learn the abstract biconditional rules or could learn about the distributional statistics of the surface elements (e.g. bigrams) composing the study items. Test strings varied these two sources orthogonally. We found no evidence of abstract rule learning either in the control or amnesic groups. In contrast, both groups learned about the surface elements and tended to call test strings "grammatical" when they were composed of familiar bigrams. However, this sensitivity to bigram familiarity was significantly reduced in the amnesic compared to the control group. The results challenge the claim that implicit learning is intact in amnesia.

Amnesia↗

PubMed1999

Countermanding saccades in humans.

We used a countermanding paradigm to investigate the relationship between conflicting cues for controlling human saccades. Subjects made a saccade to a target appearing suddenly in the periphery; but on some trials, after a delay, a stop-signal was presented that instructed subjects to inhibit the saccade. As we increased this delay, subjects increasingly failed to inhibit the movement. From measurements of this relationship, and of saccadic latency in control trials, we estimated the average time needed to inhibit the saccade (the stop-signal reaction time or SSRT). SSRTs were similar across subjects, between 125 and 145 ms, and did not vary with target luminance. We then investigated a race model in which the target initiates a response preparation signal rising linearly with a rate varying randomly from trial to trial, and racing against a similarly rising signal initiated by the cue to inhibit the saccade. The first process to cross a trigger threshold determines whether the saccade is initiated or not. In Monte Carlo simulations, this model correctly predicted the probability of successful saccade inhibition as a function of the stop-signal delay, and also the statistical distributions of saccadic latency during trials in which a stop-signal was presented but the subject failed to inhibit the saccade. These findings provide a comparison to results previously described in the monkey, and show that a simple race model with a linear rise to threshold may underlie behavioural performance in tasks of this kind.

Adolescent↗

PubMed1997

Urinary 1-hydroxypyrene as a marker of exposure to pyrene: an epidemiological survey on a general population group.

Urinary levels of 1-hydroxypyrene in a general adult population group are studied. Experimental data are not normally distributed; statistical analysis required a base 10 logarithmic transformation of data. The concentrations of urinary 1-hydroxypyrene measured were expressed as microgram g-1 urinary creatinine and are comparable with those reported by other authors, both for smoker and non-smoker subgroups. Multiple regression analysis shows that, for smokers, the number of cigarettes smoked per day and the body mass index (BMI) significantly influence the levels of urinary 1-hydroxypyrene expressed as microgram g-1 urinary creatinine, whereas no personal or behavioural variable (age, sex, alcohol consumption, dietary intake of pyrene, BMI) modified the 1-hydroxypyrene levels for non-smokers.

Adult↗