Analytical morphometry of sagittal fronto-facial profiles of 2nd-6th month human foetus

A prominent problem in the morphological study of developing biological structures is shape parametrization with the aim to evaluate transformations in a non subjective way. We carried out an analytical morphometrical study on a series of human embryos, by means of the S.A.M. (Shape Analytical Morphometry) software package. After standardization and normalization of the fronto-facial sagittal profiles, the analytical procedures applied were: 1) Fourier analysis: each profile was considered as an irregular but periodic function obtained by the sum of sinusoids of increasing order. 2) Shape Asymmetry Evaluation: couples of profiles are compared by means of "Janus" procedure; by a parabolic fitting we obtained parameters able to evaluate allometric and isometric differences between the two profiles. The preliminary results of the applied procedures indicated that rate and direction of allometric and isometric growth are not constant during the time.     

Analysis of Telemetric Time Series data for Periodic Components Using Dq-Fit

DQ-FIT and CV-SORT have been developed to facilitate the automatic analysis of data sampled by radiotelemetry, but they can also be used with other data sampled in chronobiological settings. After import of data, DQ-FIT performs conventional linear, as well as rhythm analysis according to user-defined specifications. Linear analysis includes calculation of mean values, load values (percentage of values above a defined limit), highest and lowest readings, and areas under the (parameter-time) curve (AUC). All of these parameters are calculated for the total sampling interval and for user-defined day and night periods. Rhythm analysis is performed by fitting of partial Fourier series with up to six harmonics. The contribution of each harmonic to the overall variation of data is tested statistically; only those components are included in the best-fit function that contribute significantly. Parameters calculated in DQ-FIT's rhythm analysis include mesor, amplitudes, and acrophases of all rhythmic components; significance and percentage rhythm of the combined best fit; maximum and minimum of the fitted curve and times of their occurrence. In addition, DQ-FIT uses the first derivative of the fitted curve (i.e., its slope) to determine the time and extent of maximal increases and decreases within the total sampling interval or user-defined intervals of interest, such as the times of lights on or off. CV-SORT can be used to create tables or graphs from groups of data sets analyzed by DQ-FIT. Graphs are created in CV-SORT by calculation of group mean profiles from individual best-fit curves rather than their curve parameters. This approach allows the user to combine data sets that differ in the number and/ or period length of harmonics included. In conclusion, DQ-FIT and CV-SORT can be helpful in the analysis of time-dependent data sampled by telemetry or other monitoring systems. The software can be obtained on request by every interested researcher. (Chronobiology International, 14(6), 561–574, 1997)     

Size and shape of the human first permanent molar: a Fourier analysis of the occlusal and equatorial outlines

Form can be viewed as a combination of size and shape. Shape refers to the boundary outline independently from its orientation, relation to reference planes, and dimension (or size). Shape and its changes could be quantified by mathematical methods such as the Fourier series. In this investigation, Fourier analysis has been used to quantify the morphologic characteristics (size and shape) of the outline of the occlusal surface and maximum circumference (equator) in 259 normal, healthy human first permanent maxillary and mandibular molars and to assess the effect of sex. Large within-group variability was found in the Fourier coefficients. Both equatorial and occlusal molar areas were on average larger in male than in female homologous teeth, but the difference was statistically significant only for the equatorial areas. The mean ratios between equatorial and occlusal dental areas were independent from arch (maxillary and mandibular), side, or sex. Both equatorial and occlusal outlines of left and right homologous molars within sex and arch were similar, without size and shape differences. Similarly, no sex differences in shape were found in the comparison of homologous teeth. The method used in the present study could supply information about dental shape in both its entirety and local variations. In particular, the method is extremely sensitive to local variations in dental shape, and it could be usefully employed to compare single teeth to a standard.     

Judgment algorithm for periodicity of time series data based on Bayesian information criterion

Judgment periodicity of biological time series data is important and done widely to find the circadian expression of genes, monthly change of hormones, etc. To keep complete reproducibility of judgment is a problem because popular judgment methods such as curve fitting, Fourier analysis, etc. need judgment criteria determined by analysts considering experimental conditions and results (level, S/N, distribution, etc.) based on their experience. Judgment results are often affected by analysts' subjects. Reproducible criterion determination is therefore strongly needed. We propose introducing the information criterion to replace analysts' criteria. A judgment algorithm by combining Bayesian information criterion (BIC) and discrete Fourier transform (DFT) has been developed and has proved its ability through application to mice microarray data and finding of circadian genes. Our method, named "Piccolo", shows higher sensitivity than the simple DFT (without BIC) method with reproducibility, and can be fully automated.     

Dysregulation of circadian rhythms following prolactin-secreting pituitary microadenoma

A patient who developed an irregular sleep-wake pattern following prolactin-secreting pituitary microadenoma is described. The patient reported difficulties in sleep onset and awakening at the desired time, which caused major dysfunction in his daily life activities. Despite these difficulties, the sleep-related complaints of the patient remained unrecognized for as long as three yrs. Statistical analyses of the patient's rest-activity patterns revealed that the disruption of the sleep-wake circadian rhythm originated from a disharmony between ultradian (semicircadian) and circadian components. The circadian component displayed shorter than 24 h periodicity most of the time, but the semicircadian component fluctuated between longer and shorter than 12 h periods. Additionally, desynchrony in terms of period length was found in the tentative analyses of the rest-activity pattern, salivary melatonin, and oral temperature. While the salivary melatonin time series data could be characterized by a best-fit cosine curve of 24 h, the time series data of oral temperature was more compatible with 28 h best-fit curve. The rest-activity cycle during the simultaneous measurements, however, was best approximated by a best-fit curve of 21 h. The dysregulation of circadian rhythms occurred concomitantly, but not beforehand, with the onset of pituitary disease, thus suggesting an association between the two phenomena. This association may have interesting implications to the modeling of the circadian time-keeping system. This case also highlights the need to raise the awareness to circadian rhythm sleep disorders and to consider disruptions of sleep-wake cycle in patients with pituitary adenoma.     

Nuclear morphometry and estrogen receptors in infiltrating ductal carcinoma of the breast

In this study ten cases of breast infiltrating ductal carcinoma have been considered. In all of them the content of ER has been evaluated by using monoclonal antibodies. Five of them were ER positive and five were ER negative. For the morphometric study ten nuclei of each case have been considered. By using the S.A.M. (Shape Analytical Morphometry) work-station an analytical study of the nuclear shape was performed. The first step was the extraction of fundamental shape which describes the basic shape of original contour without its irregularities. It was obtained by using two parametric equations. The second step was the evaluation of shape asymmetry by S.A.E. (Shape Asymmetry Evaluator). Finally the contour irregularities were evaluated by Fourier analysis. Along with analytical parameters, dimensions (area, perimeter and maximum diameter) were considered too. All obtained data were submitted to univariate statistical analysis (Student's T test) to compare the two groups (ER positive and ER negative tumors). Area, perimeter and maximum diameter were significatively greater in ER negative cases while analytical parameters were not discriminant between the two groups.     

Fast and accurate fitting of relaxation dispersion data using the flexible software package GLOVE

Relaxation dispersion spectroscopy is one of the most widely used techniques for the analysis of protein dynamics. To obtain a detailed understanding of the protein function from the view point of dynamics, it is essential to fit relaxation dispersion data accurately. The grid search method is commonly used for relaxation dispersion curve fits, but it does not always find the global minimum that provides the best-fit parameter set. Also, the fitting quality does not always improve with increase of the grid size although the computational time becomes longer. This is because relaxation dispersion curve fitting suffers from a local minimum problem, which is a general problem in non-linear least squares curve fitting. Therefore, in order to fit relaxation dispersion data rapidly and accurately, we developed a new fitting program called GLOVE that minimizes global and local parameters alternately, and incorporates a Monte-Carlo minimization method that enables fitting parameters to pass through local minima with low computational cost. GLOVE also implements a random search method, which sets up initial parameter values randomly within user-defined ranges. We demonstrate here that the combined use of the three methods can find the global minimum more rapidly and more accurately than grid search alone.     

Aspects of line-fitting in bivariate allometric analyses

One of the fundamental problems involved in analyses of the scaling effects of body size (allometric analysis is the choice of an appropriate best-fit line in bivariate logarithmic plots. Following a discussion of some basic aspects of allometric analysis, the tow mai procedures for the determination of a best-fit line - the least-squares regression and the major axis - are examined with respect to their different properties and underlying models. It is important to distinguish intraspecific from interspecific scaling and to recognize the distinction between use of a best-fit line to define a relationship and use of the line for prediction. An alternative model to the bivariate normal distribution, referred to as the 'extruded normal distribution', is presented and its implications are examined with respect to two test cases (scaling of basal metabolic rate in human males; scaling of population density in mammals).     

Estimation of hematocrit profile symmetry recovery length downstream from a bifurcation

Downstream from a microvascular bifurcation the distribution of blood cells in the vessel lumen is not symmetric. A diffusion process is used to model the rearrangement of red cells as blood flows between junctions in the microcirculation. A Fourier series approach is used to solve the model diffusion convection equation in slit geometry. Both flat and parabolic velocity profiles are considered. The eigenvalues, found using the Rayleigh-Ritz method, are used to find an upper bound on distance required for a symmetric red cell distribution to be obtained. The method has also been applied to cylindrical geometry and the computed symmetry recovery lengths are compared to distances between bifurcations measured in vivo. These estimates indicate that red cell distributions are frequently asymmetric in the microcirculation. Such asymmetries can have a strong effect on plasma skimming and material balance calculations.     

三峡库区低山丘陵区多尺度景观指数响应及适宜粒度

景观格局具有典型的空间异质性和尺度依赖性。在对景观格局进行分析研究时需跨越多个尺度,空间粒度大小在尺度聚合分析中至关重要。三峡库区低山丘陵区斑块破碎、景观格复杂性显著、景观格局特征及尺度变异规律仍待明确,本文以三峡库区秭归县为研究区,设定1—400m内23个粒度梯度水平,定量评估县域、乡镇以及小流域不同幅度上的景观格局指数以及拟合函数,探讨多空间幅度景观格局指数随粒度大小的变化特征。基于景观指数的粒度效应特征和拟合函数的曲线特征(最大曲率点、极值点),明确适宜不同幅度的山地景观格局指数研究的粒度阈值,以揭示库区低山丘陵区景观结构的复杂性和变异性。结果表明：不同景观指数对空间粒度变化和空间幅度变化的响应存在差异,不同景观指数的空间粒度响应主要呈现增加、降低、波动和无明显规律变化的趋势,其中斑块密度、最大斑块面积等指数对斑块形状和大小的变化敏感,而多样性指数的粒度变化敏感度较低;部分指数如斑块密度、边缘密度、周长面积分维数等对空间幅度的变化并不敏感,而最大斑块面积、景观形状指数、散布与并列指数、分离度等指数对空间幅度的变化敏感,适合进行不同幅度适宜粒度阈值的推定;边缘密度、平均斑块大小、景...     

Electric field pulses induce reversible shape transformation of human erythrocytes

Electric field pulses >2-3 kV cm¹ long known to induce membrane poration and fusion of erythrocytes as well as to enhance the transbilayer mobility of phospholipids and to perturb aminophospholipid asymmetry, are shown to induce, at 0 C., transformation of the discocytic cells into echinocytes and spheroechinocytes. The extent of transformation increases with strength, duration and number of pulses. Its time course is biphasic., a major rapid phase (t/2 ～ 5 s) being followed by a minor one, lasting for 2-3 h. Shape transformation goes along with the exofacial exposure of phosphatidylserine (PS), detected by FITC-annexin V binding and quantified by a calibration curve established via externally inserted dilauroylphosphatldylserine. Incubation of these echinocytes at 37 C leads to a rapid recovery of the discocytic shape followed by slower formation of stomatocytes. Shape recovery is temperature dependent (E_a ～100 kJ/mol), and can be impaired by depletion of ATP or Mg⁺⁺ and by addition of vanadate or fluoride. Shape recovery and stomatocyte formation go along with a rapid loss of annexin binding in about 45% of the cells while the rest maintains its binding capacity. In the presence of vanadate, annexin binding increases in all cells. The results are discussed in the light of the bilayer couple concept of erythrocyte shape and the enhanced transverse mobility of phospholipids. Echinocyte formation is most likely caused by the reorientation of endofacial aminopho-spholipids to the outer leaflet of the bilayer. Shape recovery and stomatocyte formation probably result from a continuous reinternalization of PS via the ATP dependent aminophospholipid translocase, but may also be supported by downhill movement of PC to the inner leaflet and by other yet unidentified processes.     

Evaluation and statistical judgement of neural responses to sinusoidal stimulation in cases with superimposed drift and noise

Time histograms of neural responses evoked by sinusoidal stimulation often contain a slow drifting and an irregular noise which disturb Fourier analysis of these responses. Section 2 of this paper evaluates the extent to which a linear drift influences the Fourier analysis, and develops a combined Fourier and linear regression analysis for detecting and correcting for such a linear drift. Usefulness of this correcting method is demonstrated for the time histograms of actual eye movements and Purkinje cell discharges evoked by sinusoidal rotation of rabbits in the horizontal plane. In Sect. 3, the analysis of variance is adopted for estimating the probability of the random occurrence of the response curve extracted by Fourier analysis from noise. This method proved to be useful for avoiding false judgements as to whether the response curve was meaningful, particularly when the response was small relative to the contaminating noise.     

Reverse engineering an amyloid aggregation pathway with dimensional analysis and scaling

Human islet amyloid polypeptide (hIAPP) is a cytotoxic protein that aggregates into oligomers and fibrils that kill pancreatic β-cells. Here we analyze hIAPP aggregation in vitro, measured via thioflavin-T fluorescence. We use mass-action kinetics and scaling analysis to reconstruct the aggregation pathway, and find that the initiation step requires four hIAPP monomers. After this step, monomers join the nucleus in pairs, until the first stable nucleus (of size approximately 20 monomers) is formed. This nucleus then elongates by successive addition of single monomers. We find that the best-fit of our data is achieved when we include a secondary fibril-dependent nucleation pathway in the reaction scheme. We predict how interventions that change rates of fibril elongation or nucleation rates affect the accumulation of potentially cytotoxic oligomer species. Our results demonstrate the power of scaling analysis in reverse engineering biochemical aggregation pathways.     

Understanding and predicting strain-specific patterns of pathogenesis in the rodent malaria Plasmodium chabaudi

Despite considerable success elucidating important immunological and resource-based mechanisms that control the dynamics of infection in some diseases, little is known about how differences in these mechanisms result in strain differences in patterns of pathogenesis. Using a combination of data and theory, we disentangle the role of ecological factors (e.g., resource abundance) in the dynamics of pathogenesis for the malaria species Plasmodium chabaudi in CD4+ T cell-depleted mice. We build a series of nested models to systematically test a number of potential regulatory mechanisms and determine the "best" model using statistical techniques. The best-fit model is further tested using an independent data set from mixed-clone competition experiments. We find that parasites preferentially invade older red blood cells even when they are more fecund in younger reticulocytes and that inoculum size has a strong effect on burst size in reticulocytes. Importantly, the results suggest that strain-specific differences in virulence arise from differences in red blood cell age-specific invasion rates and burst sizes, since these are lower for the less virulent strain, as well as from differences in levels of erythropoesis induced by each strain. Our analyses highlight the importance of model selection and validation for revealing new biological insights.     

When morphometry meets genetics: inferring the phylogeography of Carabus solieri using Fourier analyses of pronotum and male genitalia

Population differentiation is a crucial step in the speciation process and is therefore a central subject in studies of microevolution. Assessing divergence and inferring its dynamics in space and time generally require a wide array of markers. Until now however, most studies of population structure are based on molecular markers and those concerning morphological traits are more scarce. In the present work, we studied morphological differentiation among populations of the ground beetle Carabus solieri, and tested its congruence with genetic population structure. The shape of pronotum and aedeagus was assessed using Dual Axis Fourier Shape Analysis. manova on Fourier coefficients revealed highly significant morphological variation between populations and a similar geographical pattern of differentiation for both structures. On the whole, morphological and genetic patterns were also found to be congruent. Our analysis confirms the phylogeographical scenario proposing that two entities of C. solieri differentiated during the last glaciation events before recolonizing the actual range of the species. It also indicates a large introgression between the two differentiated entities in the centre of the range.